Process for preparing pyrazoles

ABSTRACT

The present invention relates to a process for preparing a pyrazole compound of formula V, the process including cyclizing a hydrazone substituted α,β-unsaturated carbonyl compound of formula IV by reacting it with a suitable reagent, e.g. a reducing agent, an organometallic reagent or a nucleophilic reagent. The compounds of formula V are versatile reaction tools for the preparation of pyrazole derived fine chemicals. The present invention also relates to pyrazole compounds of formulae Va, Vb, Vc, and VI.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Phase Application ofPCT/EP2015/067507, filed Jul. 30, 2015, which claims the benefit ofpriority to EP application 14179249.9, filed Jul. 31, 2014, the contentsof which are hereby expressly incorporated by reference in theirentirety.

The present invention relates to a process for preparing a pyrazolecompound according to the following reaction sequence:

In particular, the present invention is directed to a process ofpreparing a pyrazole compound of formula V, which comprises cyclizing ahydrazone substituted α,β-unsaturated carbonyl compound of formula IV byreacting it with a suitable reagent, e.g. a reducing agent, anorganometallic reagent or a nucleophilic reagent (step (c)). The processmay further comprise preparing the hydrazone substituted α,β-unsaturatedcarbonyl compound of formula IV by reacting an α,β-unsaturated carbonylcompound of formula III, which contains a leaving group in theβ-position, with a hydrazone compound of formula II (step (b)), andpreparing said hydrazone compound of formula II by reacting a carbonylcompound of formula I with hydrazine (step (a)).

The process of the present invention may further comprise steps ofconverting certain 4-substituted pyrazole compounds into activated4-pyrazole carboxylic acid derivatives according to the followingreaction sequence:

In particular, the process of the invention may optionally furthercomprise converting a pyrazole compound of formula Va, which comprisesan ester group in the 4-position, or a pyrazole compound of formula Vb,which comprises a cyano group in the 4-position, into a 4-pyrazolecarboxylic acid compound of formula Vc (step (d)). Moreover, the processmay further comprise converting a 4-pyrazole carboxylic acid compound offormula Vc into an activated 4-pyrazole carboxylic acid derivative offormula VI (step (e)).

The process of the present invention may still further comprise the stepof converting 4-activated pyrazole carboxylic acid derivatives into4-pyrazole N-(het)arylamide compounds, which are known as pesticidallyactive compounds, according to the following reaction:

In particular, the process may still further comprise the step ofreacting an activated 4-pyrazole carboxylic acid derivative of formulaVI with a suitable N-(het)arylamine compound of formula VII to yield a4-pyrazole N-(het)arylamide compound of formula VIII (step (f)).

The present invention also relates to novel pyrazole compounds offormulae Va, Vb, Vc and VI.

Pyrazole compounds, in particular 4-pyrazole carboxylic acidderivatives, such as esters, nitriles, acids and activated acidderivatives, are versatile intermediate compounds for the preparation ofpyrazole derived fine chemicals, such as compounds in the pharmaceuticalor agrochemical field. In particular the compounds are versatileintermediate compounds for the preparation of pyrazole derivedpesticides, such as 4-pyrazole N-(het)arylamide compounds, which areknown to be particularly useful for combating invertebrate pests (see WO2009/027393, WO 2010/034737, WO 2010/034738, and WO 2010/112177). Ofparticular interest are pyrazole compounds and 4-pyrazole carboxylicacid derivatives, which are substituted at one nitrogen atom andoptionally also substituted in the 3- and/or 5-position because also thepyrazole derived pesticides including the above mentioned 4-pyrazoleamide compounds often comprise pyrazole moieties, which are substitutedaccordingly.

In view of the above, there is a need for a process for preparingN-substituted pyrazole compounds and optionally further converting theminto pyrazole derived pesticides. A particular problem accompanying thepreparation of N-substituted pyrazole compounds is the regioselectivity,if substituents are present in the 3- and/or 5-position of the pyrazolering, in particular, if a substituent is present in the 3-position, butnot in the 5-position, if a substituent is present in the 5-position,but not in the 3-position, or if different substituents are present inthe 3- and 5-position. Accordingly, there is a particular need for aprocess for regioselectively preparing N-substituted pyrazole compounds,which have a substituent either in the 3- or in the 5-position ordifferent substituents in the 3- and 5-position of the pyrazole ring. Inview of the preparation of 4-pyrazole N-(het)arylamide compounds aspesticides, such a process should particularly be suitable forregioselectively obtaining N-substituted 4-pyrazole carboxylic acidderivatives, which have a substituent either in the 3- or in the5-position or different substituents in the 3- and 5-position of thepyrazole ring.

It is noted that the numbering of the atoms of an N-substituted pyrazolecompound is usually as follows.

The positions of the substituents are indicated by the same numbers. Thesubstituent at the nitrogen atom is typically referred to as theN-substituent rather than as substituent in the 1-position, althoughthis is also suitable. The 2-position, i.e. the second nitrogen atom ofthe N-substituted pyrazole compounds, is typically unsubstituted. Incontrast, the 3-, 4- and 5-positions may each be substituted.

There are principally two processes known for the preparation ofN-substituted 4-pyrazole carboxylic acid derivatives, which are 3-and/or 5-substituted.

Firstly, such N-substituted 4-pyrazole carboxylic acid derivatives canbe prepared by reacting an α,β-unsaturated carbonyl compound, e.g. anα,β-unsaturated ketone, which contains a leaving group in theβ-position, with a hydrazine derivative, which has a substituent at oneof the two nitrogen atoms. In view of the fact that the substitutedhydrazine derivative comprises two amino groups, which are often verysimilar in terms of their nucleophilic reactivity, two regioisomers ofthe desired N-substituted pyrazole compound are usually obtained becauseeither the substituted nitrogen atom or the unsubstituted nitrogen atomof the hydrazine derivative may react. Reactions, wherein thesubstituted hydrazine derivatives are used in the form of salts, havealready been described, e.g., in JP 2007/326784, WO 2010/142628, and WO2012/019015, and reactions, wherein mono-protected substituted hydrazinederivatives are used, have been described in WO 2012/019015. However,the regioselectivity problem in terms of the 3-/5-substitution patternof the resulting N-substituted 4-pyrazole carboxylic acid derivativescould not be solved.

Secondly, N-substituted 4-pyrazole carboxylic acid derivatives, whichare 3- and/or 5-substituted, can be prepared by reacting anα,β-unsaturated carbonyl compound, e.g. an α,β-unsaturated ketone, whichcontains a leaving group in the β-position, with hydrazine and thenN-alkylating the resulting pyrazole derivative. Due to the tautomerismof the pyrazole compound, which is obtained as an intermediate, tworegioisomers of the desired N-substituted pyrazole compound are usuallyobtained upon alkylation. Such reaction sequences have, e.g., beendescribed in Heterocycles 2000, 2775, Liebigs Analen der Chemie 1985,794, or Journal of Heterocyclic Chemistry 1985, 1109.

A process for regioselectively preparing N-substituted 4-pyrazolecarboxylic acid derivatives, which are 3-substituted or 3- and5-substituted with different substituents, was published by Glorius etal. in Angew. Chem. Int. Ed. 2010, 7790, and Green Chem. 2012, 14, 2193.Said process is performed by reacting an enamine compound with an excessof a suitable nitrile compound in the presence of stoichiometric orcatalytic amounts of copper.

Although the process regioselectively provides N-substituted 4-pyrazolecarboxylic acid derivatives, which are 3-substituted or 3- and5-substituted with different substituents, the process isdisadvantageous in that copper is involved as a heavy metal, and anexcess of at least three equivalents of the nitrile compound has to beused, so that the process is not environmentally friendly and noteconomical. Furthermore, the process has not been described for HCN asnitrile compound, most likely for the reason that HCN would polymerizeunder the reaction conditions, so that a cyclization reaction with theenamine compound according to the above reaction scheme would not takeplace. As a consequence, N-substituted 4-pyrazole carboxylic acidderivatives, which are 5-substituted, but not 3-substituted, canobviously not be obtained according to the process described by Gloriuset al.

In view of the above, it is an object of the invention to provide aprocess for preparing N-substituted pyrazole compounds and optionallyfurther converting them into pyrazole derived pesticides. In particular,it is an object to provide a process for preparing N-substitutedpyrazole compounds, which are substituted e.g. in the 3- and/or5-position and/or in the 4-position, wherein these substituents may beidentical or different, preferably different.

It is another object of the invention to provide a process forregioselectively preparing N-substituted pyrazole compounds, which are3- and/or 5-substituted. In particular, it is an object to provideregioselective access to a variety of N-substituted pyrazole compounds,which are 3-substituted, 5-substituted or 3- and 5-substituted withdifferent substituents, and preferably 5-substituted, but not3-substituted.

It is yet another object of the invention to provide a process forregioselectively preparing N-substituted 4-pyrazole carboxylic acidderivatives, for example esters or nitriles, which are 3- and/or5-substituted. In particular, it is an object to provide regioselectiveaccess to a variety of N-substituted 4-pyrazole carboxylic acidderivatives, which are 3-substituted, 5-substituted or 3- and5-substituted with different substituents, and preferably 5-substituted,but not 3-substituted.

In connection with the above objects, it is a further object to providea process, which can be performed from readily and cheaply availablestarting materials. Furthermore, it is an object in connection with theabove objects to provide a process, which is economical in terms of theyields and the amounts of the reactants, which are reacted with eachother. Moreover, it is an object in connection with the above objects toprovide a process, which is suitable for a technical scale.

It is yet another object of the invention to provide a process, whichfurther allows for the provision of the free N-substituted 4-pyrazolecarboxylic acids and activated derivatives thereof, wherein saidcompounds are preferably 3- and/or 5-substituted, e.g. 3-substituted,5-substituted or 3- and 5-substituted with different substituents, andparticularly preferably 5-substituted, but not 3-substituted.

It is yet another object of the invention to provide a process, whichfurther allows for the provision of N-substituted 4-pyrazole amides,wherein the pyrazole moiety is preferably 3- and/or 5-substituted, e.g.3-substituted, 5-substituted or 3- and 5-substituted with differentsubstituents, and particularly preferably 5-substituted, but not3-substituted.

Furthermore, it is an object of the invention to provide N-substituted4-pyrazole carboxylic acid derivatives, for example esters or nitriles,N-substituted 4-pyrazole carboxylic acids and activated derivativesthereof, which may in each case be 3- and/or 5-substituted, e.g.3-substituted, 5-substituted or 3- and 5-substituted with differentsubstituents, and preferably 5-substituted, but not 3-substituted. Inparticular, it is an object to provide N-substituted 4-pyrazolecarboxylic acid derivatives, N-substituted 4-pyrazole carboxylic acidsand activated derivatives thereof, which have specific N-substituentsand specific substituents in the 5-position, but are unsubstituted inthe 3-position, because such pyrazole compounds are suitable for thepreparation of 4-pyrazole N-(het)arylamide compounds with anexceptionally high pesticidally activity.

The above objects are achieved by the processes and compounds describedin detail in the claims and hereinafter.

In one aspect, the present invention relates to preparing a pyrazolecompound of formula V or a salt, stereoisomer, tautomer or N-oxidethereof

comprising the step of cyclizing a hydrazone substituted α,β-unsaturatedcarbonyl compound of formula IV

by reacting it with a reagent comprising a R⁶ group,wherein

-   R¹ is selected from H, halogen, CN, NO₂, C₁-C₁₀-alkyl,    C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms be    unsubstituted, may be partially or fully halogenated or may be    substituted by 1, 2, or 3 identical or different substituents R^(x);    -   OR^(a), SR^(a), C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y¹R^(d),        NR^(e)R^(f), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl,        C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl and aryl, wherein the        cyclic moieties may be unsubstituted or substituted by 1, 2, 3,        4, or 5 identical or different substituents selected from the        radicals R^(y) and R^(x);-   R² is selected from H, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl,    wherein the C-atoms may be unsubstituted, may be partially or fully    halogenated or may be substituted by 1, 2, or 3 identical or    different substituents R^(x);    -   C(Y)OR^(c), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl,        C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl and aryl, wherein the        cyclic moieties may be unsubstituted or may be substituted by 1,        2, 3, 4, or 5 identical or different substituents selected from        the radicals R^(y) and R^(x); and-   R³ is selected from H, halogen, CN, NO₂, C₁-C₁₀-alkyl,    C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms may be    unsubstituted, may be partially or fully halogenated or may be    substituted by 1, 2, or 3 identical or different substituents R^(x);    -   OR^(a), SR^(a), C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y¹R^(d),        NR^(e)R^(f), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl,        C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl and aryl, wherein the        cyclic moieties may be unsubstituted or may be substituted by 1,        2, 3, 4, or 5 identical or different substituents selected from        the radicals R^(y) and R^(x);        and wherein-   R⁴ and R⁵ are independently of each other selected from H, NO₂,    C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms    may be unsubstituted, may be partially or fully halogenated or may    be substituted by 1, 2 or 3 identical or different substituents    R^(x);    -   C₁-C₁₀-haloalkyl, C₁-C₄-alkoxy-C₁-C₁₀-alkyl, wherein the C-atoms        may be unsubstituted, or partially or fully substituted by        identical or different substituents R^(y);    -   C(Y)OR^(c), C(Y)NR^(g)R^(h), C(Y)NR^(i)NR^(e)R^(f),        C₁-C₅-alkylen-OR^(a), C₁-C₅-alkylen-CN,        C₁-C₅-alkylen-C(Y)OR^(c), C₁-C₅-alkylen-NR^(e)R^(f),        C₁-C₅-alkylen-C(Y)NR^(g)R^(h), C₁-C₅-alkylen-S(O)_(m)R^(d),        C₁-C₅-alkylen-S(O)_(m)NR^(e)R^(f),        C₁-C₅-alkylen-NR^(i)NR^(e)R^(f);    -   heterocyclyl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl, hetaryl,        aryl, heterocyclyl-C₁-C₅-alkyl, C₃-C₁₀-cycloalkyl-C₁-C₅-alkyl,        C₃-C₁₀-cycloalkenyl-C₁-C₅-alkyl, hetaryl-C₁-C₅-alkyl,        aryl-C₁-C₅-alkyl, wherein the cyclic moieties may be        unsubstituted or may be substituted by 1, 2, 3, 4, or 5        identical or different substituents R^(y);    -   groups -D-E, wherein        -   D is a direct bond, C₁-C₆-alkylene, C₂-C₆-alkenylene, or            C₂-C₆-alkynylene, which carbon chains can be partially or            fully substituted by R^(n), and        -   E is a non-aromatic 3- to 12-membered carbo- or heterocycle,            which may contain 1, 2, 3, or 4 heteroatoms selected from            N—R^(l), O, and S, wherein S may be oxidized, which carbo-            or heterocycle may be partially or fully substituted by            R^(n);    -   and    -   groups -A-SO_(m)-G, wherein        -   A is C₁-C₆-alkylene, C₂-C₆-alkenylene and C₂-C₆-alkynylene,            wherein the C-atoms may be unsubstituted, or partially or            fully substituted by R^(p), and        -   G is C₁-C₄-haloalkyl or C₃-C₆-cycloalkyl which may be            halogenated;            or-   R⁴ and R⁵ together with the carbon atom to which they are attached    form a 3- to 12-membered non-aromatic carbo- or heterocycle, which    heterocycle may contain 1, 2, 3, 4, or 5 heteroatoms selected from    N—R^(l), O, and S, wherein S may be oxidized, and which carbo- or    heterocycle may be partially or fully substituted by R^(j);    and wherein-   R⁶ is selected from H, CN, C₁-C₆-fluoroalkyl, C₁-C₆-alkyl,    C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl,    C₃-C₆-cycloalkyl-C₁-C₂-alkyl, C₃-C₆-cycloalkenyl,    C₃-C₆-cycloalkenyl-C₁-C₂-alkyl, heterocyclyl,    heterocyclyl-C₁-C₂-alkyl, aryl, aryl-C₁-C₂-alkyl, hetaryl,    hetaryl-C₁-C₂-alkyl, wherein the carbon chains or cyclic moieties    may be unsubstituted, partially or fully substituted by identical or    different substituents R^(x);    -   OR^(a), SR^(a), NR^(e)R^(f), and    -   groups of general formula (i)

and wherein

-   R^(a), R^(b) are independently of each other selected from H,    C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl,    C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl,    C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl,    C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,    heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl,    aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the cyclic    moieties may be unsubstituted or may be substituted by 1, 2, 3, 4,    or 5 substituents which, independently of each other, are selected    from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₁-C₄-alkoxy and C₁-C₄-haloalkoxy;-   R^(c) is selected from H, C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl,    C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkylmethyl, C₃-C₁₀-halocycloalkyl,    C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl,    C₃-C₆-halocycloalkenyl, C₂-C₁₀-alkenyl, C₂-C₁₀-haloalkenyl,    C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl,    heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and    hetaryl-C₁-C₄-alkyl, wherein the ring in the six last mentioned    radicals may be unsubstituted or may be substituted by 1, 2, 3, 4,    or 5 substituents which, independently of each other, are selected    from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; or-   R^(c) together with the C(Y)O group forms a salt [C(Y)O]⁻NR₄ ⁺,    [C(Y)O]⁻M_(a) ⁺ or [C(Y)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali    metal and M_(ea) is an alkaline earth metal, and wherein the    substituents R at the nitrogen atom are independently of each other    selected from H, C₁-C₁₀-alkyl, phenyl and phenyl-C₁-C₄-alkyl;-   R^(d) is selected from C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₃-C₆-cycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl,    C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl,    C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl,    C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl,    heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and    hetaryl-C₁-C₄-alkyl, wherein the cyclic moieties may be    unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents    which are independently of each other selected from halogen, CN,    C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and    C₁-C₄-haloalkoxy;-   R^(e), R^(f) are independently of each other selected from H,    C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl,    C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl,    C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl,    C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,    C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkylsulfonyl,    C₁-C₄-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl,    heterocyclylcarbonyl, heterocyclyl-C₁-C₄-sulfonyl, aryl,    arylcarbonyl, arylsulfonyl, hetaryl, hetarylcarbonyl,    hetarylsulfonyl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein    the cyclic moieties may be unsubstituted or may be substituted by 1,    2, 3, 4, or 5 substituents which, independently of each other, are    selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; or-   R^(e) and R^(f) together with the N atom to which they are bonded    form a 5- or 6-membered, saturated or unsaturated heterocycle, which    may comprise a further heteroatom being selected from O, S and N as    a ring member atom and wherein the heterocycle may be unsubstituted    or may by substituted by 1, 2, 3, 4, or 5 substituents which are    independently of each other selected from halogen, CN, C(O)NH₂, NO₂,    C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy;-   R^(g), R^(h) are independently of each other selected from H,    C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl,    C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-halocycloalkenyl,    C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl,    C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl,    aryl, hetaryl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the    cyclic moieties may be unsubstituted or may be substituted by 1, 2,    3, 4, or 5 substituents which are independently of each other    selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy;-   R^(i) is selected from H, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₃-C₆-cycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl,    C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl,    C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl,    C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, aryl, aryl-C₁-C₄-alkyl,    wherein the aryl ring may be unsubstituted or may be substituted by    1, 2, 3, 4, or 5 substituents which are independently of each other    selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy;-   R^(j) is halogen, OH, CN, C(O)NH₂, NO₂, C₁-C₁₀-alkyl,    C₁-C₁₀-haloalkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-haloalkoxy, benzyloxy,    S(O)_(m)R^(k), C₃-C₆-cycloalkyl, or a 3- to 6-membered heterocycle,    which may contain 1 or 2 heteroatoms selected from N—R^(l), O, and    S, wherein S may be oxidized, which R^(j) groups are unsubstituted    or partially or fully substituted by R^(m), and wherein two groups    R^(j) connected to the same or adjacent ring atoms may together form    a 3- to 6-membered carbo- or heterocycle which heterocycle may    contain 1 or 2 heteroatoms selected from N—R^(l), O, and S, wherein    S may be oxidized, which cycles may be partially or fully    substituted by R^(m) radicals;-   R^(k) is H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, or C₃-C₆-cycloalkyl, which    cycle may be partially or fully substituted by R^(l);-   R^(l) is H, halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₁-C₄-alkylcarbonyl, or C₁-C₄-alkoxycarbonyl;-   R^(m) is halogen, OH, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    or S(O)_(m)R^(k);-   R^(n) is halogen, CN, C(Y)OR^(c), C(O)NH₂, NO₂, C₁-C₂-alkyl,    C₁-C₄-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl,    C₃-C₆-cycloalkenyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkyliden, or S(O)_(m)R^(o), two    adjacent groups R^(n) may form together with the atoms to which they    are bonded a 3- to 8-membered carbo- or heterocycle, which may    contain 1, 2, 3, or 4 heteroatoms selected from N—R^(l), O, and S,    wherein S may be oxidized, which cyclic R^(n) moieties may be    substituted by halogen, R^(o), or R^(l);-   R^(o) is H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, or    C₁-C₄-alkoxy;-   R^(p) is halogen, CN, C(O)NH₂, NO₂, C₁-C₂-alkyl, C₁-C₂-haloalkyl,    C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, or C₁-C₂-haloalkoxy, or two groups    R^(p) can together form a 3- to 6-membered carbo- or heterocyclic    ring, which heterocycle contains 1 or 2 heteroatoms selected from    N—R^(l), O, and S, wherein S may be oxidized, which carbo- or    heterocyclic ring is unsubstituted or partly or fully substituted by    groups R^(q);-   R^(q) is halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl,    C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy;-   R^(r) and R^(s) are independently of each other selected from R^(b),    OR^(c1), and NR^(g)R^(h);-   R^(c1) is C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₃-C₁₀-cycloalkyl,    C₃-C₁₀-cycloalkylmethyl, C₃-C₁₀-halocycloalkyl, C₃-C₆-cycloalkenyl,    C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₁₀-alkenyl,    C₂-C₁₀-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,    heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl,    aryl-C₁-C₄-alkyl or hetaryl-C₁-C₄-alkyl, wherein the ring in the six    last mentioned radicals may be unsubstituted or may be substituted    with 1, 2, 3, 4 or substituents which, independently of each other,    are selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₁-C₄-alkoxy or C₁-C₄-haloalkoxy;-   R^(t) is H or R^(a);-   R^(x) is halogen, CN, C(Y)OR^(c), C(Y)NR^(g)R^(h), NO₂, C₁-C₄-alkyl,    C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, S(O)_(m)R^(d),    S(O)_(m)NR^(e)R^(f), C₁-C₅-alkylen-NHC(O)OR^(c),    C₁-C₁₀-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl,    C₁-C₄-haloalkoxycarbonyl, C₃-C₆-cycloalkyl, 5- to 7-membered    heterocyclyl, 5- or 6-membered hetaryl, aryl, C₃-C₆-cycloalkoxy, 3-    to 6-membered heterocyclyloxy, or aryloxy, wherein the cyclic    moieties may be unsubstituted or may be substituted by 1, 2, 3, 4,    or 5 radicals R^(y); and-   R^(y) is selected from halogen, CN, C(Y)OR^(c), C(Y)NR^(g)R^(h),    NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy,    benzyloxymethyl, S(O)_(m)R^(d), S(O)_(m)NR^(e)R^(f),    C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl,    C₁-C₄-haloalkoxycarbonyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl,    C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl and    C₁-C₄-alkoxy-C₁-C₄-alkyl;    and wherein-   Y is O or S;-   Y¹ is O, S, or N—R^(1a);-   R^(1a) is H, C₁-C₁₀-alkyl, C₃-C₁₂-cycloalkyl, aryl, or hetaryl; and-   m is 0, 1 or 2.

Preferably, formula IV is to be understood as not only covering thecompounds as such, but also as covering salts, stereoisomers, tautomersor N-oxides of the compounds of formula IV.

The process as defined above is suitable for providing a variety ofN-substituted pyrazole compounds of formula V, which may be furtherconverted to give pyrazole derived pesticides.

Furthermore, it has surprisingly been found that the process is suitablefor regioselectively preparing a variety of N-substituted pyrazolecompounds, which are 3- or 5-substituted or substituted with differentsubstituents in the 3- and 5-position. In particular, the substitutionpattern of the compounds of formula IV predefines the substitutionpattern of the resulting N-substituted pyrazole compounds, so that theproblem of regioselectivity can completely be avoided. The compound offormula IV can be selected as such, that a variety of substituents inthe 3- and/or 5- as well as in the 4-position of the N-substitutedpyrazole compounds can be realized. In this context, it has also beenfound that N-substituted 4-pyrazole carboxylic acid derivatives, whichare 3- or 5-substituted or substituted with different substituents inthe 3- and 5-position, can regioselectively be obtained by the processaccording to the present invention.

The process provides the N-substituted pyrazole compounds of formula Vin high yields based on the amounts of the compounds of formula IV.

Furthermore, it is an advantage of the process that the compounds offormula IV can be obtained from readily and cheaply available startingmaterials. In particular, it is an advantage that the compounds offormula IV can be obtained by reacting α,β-unsaturated carbonylcompounds of formula III, which contain a leaving group in theβ-position, with hydrazone compounds of formula II, wherein theα,β-unsaturated carbonyl compounds of formula III are readily availableeither commercially or by methods known in the art, and the hydrazonecompounds of formula II can easily be obtained by reacting commerciallyavailable carbonyl compounds of formula I with hydrazine. This will beoutlined in further detail below. By varying the carbonyl compounds offormula I and the α,β-unsaturated carbonyl compounds of formula III, avariety of compounds of formulae II, IV and V can thus easily beobtained.

Furthermore, the compounds of formula V can be further converted intopyrazole derived pesticides. For example, if the pyrazole compound offormula V is a pyrazole compound of formula Va or Vb with an ester or acyano group in the 4-position, said compound can easily be convertedinto the corresponding 4-pyrazole carboxylic acid compound of formulaVc. Alternatively, such 4-pyrazole carboxylic acid compounds of formulaVc may directly be obtained from suitable compounds of formula IV. Fromthe 4-pyrazole carboxylic acid compound of formula Vc, activated4-pyrazole carboxylic acid derivatives of formula VI can be obtained bystandard activation processes. The compounds of formula VI may then beconverted into 4-pyrazole N-(het)arylamide compounds of formula VIII,which may represent highly active pesticides.

In view of the above, certain preferred embodiments of the inventionrelate to a process, wherein the hydrazone substituted α,β-unsaturatedcarbonyl compound of formula IV

is prepared by reacting an α,β-unsaturated carbonyl compound of formulaIII

with a hydrazone compound of formula II

wherein

X is a leaving group

and R¹, R², R³, R⁴ and R⁵ are as defined above.

Furthermore, certain more preferred embodiments of the invention relateto a process, wherein the above hydrazone compound of formula II isprepared by reacting a carbonyl compound of formula I

with hydrazine or a salt thereof,

wherein R⁴ and R⁵ are as defined above.

Preferably, formulae I, II, III and IV are to be understood as not onlycovering the compounds as such, but also as covering salts,stereoisomers, tautomers or N-oxides of these compounds. However,N-oxides are of course only possible, if a nitrogen atom is present inthe compounds.

In view of the above, certain preferred embodiments of the inventionfurther relate to a process, wherein the compound of formula V is acompound of formula Va or Vb

and wherein said compound of formula Va or Vb is converted into acompound of formula Vc

wherein R², R³, R⁴, R⁵ and R⁶ are as defined above,

and wherein R^(c) in formula Va is C₁-C₄-alkyl or aryl-C₁-C₄-alkyl.

Preferably, formulae Va, Vb and Vc are to be understood as not onlycovering the compounds as such, but also as covering salts,stereoisomers, tautomers or N-oxides of these compounds.

Furthermore, certain preferred embodiments of the invention relate to aprocess, wherein a compound of formula Vc is converted into a compoundof formula VI

wherein X¹ is a leaving group, and wherein R², R³, R⁴, R⁵ and R⁶ are asdefined above.

With regard to X¹, it is noted that X¹ may be any leaving group,preferably a leaving group, which is suitable for amide couplingreactions.

For example, X¹ may be a leaving group, which is based on a peptidecoupling reagent. Suitable peptide coupling reagents are described byHan et al. in Tetrahedron 60 (2004) 2447-2467. In this regard,N,N′-bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (BOP—Cl) andO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) are preferred according to the presentinvention.

Furthermore, X¹ may be a leaving group selected from active esters,azide and halogens.

Preferably, X¹ is selected from halogen, N₃, p-nitrophenoxy, andpentafluorophenoxy, and is particularly preferably halogen, such as Cl.

Preferably, formula VI is again to be understood as not only coveringthe compounds as such, but also as covering salts, stereoisomers,tautomers or N-oxides of these compounds.

Moreover, certain more preferred embodiments of the invention relate toa process, wherein the above compound of formula VI is converted into acompound of formula VIII

by reacting it with a compound of formula VII

wherein R², R³, R⁴, R⁵ and R⁶ are as defined above, and wherein U is Nor CR^(U);

-   R^(P1), R^(P2), R^(P3), and R^(U) are independently of each other    selected from H, halogen, C₁-C₄-alkyl, C₁-C₃-haloalkyl,    C₁-C₄-alkoxy, C₁-C₃-haloalkoxy, C₁-C₄-alkylthio,    C₁-C₃-haloalkylthio, C₁-C₄-alkylsulfinyl, C₁-C₃-haloalkylsulfinyl,    C₁-C₄-alkylsulfonyl, C₁-C₃-haloalkylsulfonyl, C₃-C₆-cycloalkyl,    C₃-C₆-halocycloalkyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl,    C₂-C₄-alkynyl and C₁-C₄-alkoxy-C₁-C₄-alkyl; and-   R^(1N) is H, CN, C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₃-C₁₀-cycloalkyl,    C₃-C₁₀-halocycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₂-C₁₀-alkenyl,    C₂-C₁₀-haloalkenyl, C₂-C₁₀-alkynyl, C₃-C₁₀-haloalkynyl,    C₁-C₅-alkylen-CN, OR^(a), C₁-C₅-alkylen-OR^(a), C(Y)R^(b),    C₁-C₅-alkylen-C(Y)R^(b), C(Y)OR^(c), C₁-C₅-alkylen-C(Y)OR^(c),    S(O)₂R^(d), NR^(e)R^(f), C₁-C₅-alkylen-NR^(e)R^(f), C(Y)NR^(g)R^(h),    C₁-C₅-alkylen-C(Y)NR^(g)R^(h), S(O)_(m)NR^(e)R^(f),    C(Y)NR^(i)NR^(e)R^(f), C₁-C₅-alkylen-S(O)₂R^(d),    C₁-C₅-alkylen-S(O)_(m)NR^(e)R^(f),    C₁-C₅-alkylen-C(Y)NR^(i)NR^(e)R^(f), aryl, heterocyclyl, hetaryl,    aryl-C₁-C₅-alkyl, C₃-C₁₀-cycloalkyl-C₁-C₅-alkyl,    heterocyclyl-C₁-C₅-alkyl or hetaryl-C₁-C₅-alkyl, wherein the cyclic    moieties may be unsubstituted or may be substituted by 1, 2, 3, 4,    or 5 identical or different substituents selected from the radicals    R^(y) and R^(x).

Preferably, formulae VI and VIII are again to be understood as not onlycovering the compounds as such, but also as covering salts,stereoisomers, tautomers or N-oxides of these compounds.

In another aspect, the present invention relates to a compound offormula Va or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

-   -   R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is        H; or    -   R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and        R⁶ is H;

and wherein

-   -   R^(c) is C₁-C₄-alkyl or aryl-C₁-C₄-alkyl, or wherein R^(c)        together with the C(O)O group forms a salt [C(O)O]⁻NR₄ ⁺,        [C(O)O]⁻M_(a) ⁺ or [C(O)O]⁻½M_(ea) ²⁺, wherein M_(a) is an        alkali metal and M_(ea) is an alkaline earth metal; and wherein        the substituents R at the nitrogen atom are independently of        each other selected from H, C₁-C₁₀-alkyl, phenyl and        phenyl-C₁-C₄-alkyl.

In yet another aspect, the present invention relates to a compound offormula Vb or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H.

The compounds of formula Va and Vb represent precursors forN-substituted 4-pyrazole carboxylic acids Vc, which itself representversatile reaction tools for the preparation of certain 4-pyrazoleN-(het)arylamide compounds of formula VIII, which are highly activepesticides.

Thus, in another aspect, the present invention relates to a compound offormula Vc or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H.

The 4-pyrazole carboxylic acid compounds of formula Vc can easily beactivated for a subsequent amidation reaction to give the 4-pyrazoleN-(het)arylamide compounds of formula VIII.

Thus, in yet another aspect, the present invention relates to a compoundof formula VI or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

-   -   R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or    -   R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is        H; or    -   R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and        R⁶ is H;

and wherein

-   -   X¹ is a leaving group, which is preferably selected from        halogen, N₃, p-nitrophenoxy, and pentafluorophenoxy, and which        is particularly preferably Cl.

The compounds of formula VI represent activated species, which caneither be formed in situ or isolated after activation of the 4-pyrazolecarboxylic acid compounds of formula Vc, and which can be easilyconverted into the 4-pyrazole N-(het)arylamide compounds of formula VIIIby reacting them with a suitable N-(het)arylamine.

Further embodiments of the present invention can be found in the claims,the description and the examples. It is to be understood that thefeatures mentioned above and those still to be illustrated below of thesubject matter of the invention can be applied not only in therespective given combination but also in other combinations withoutleaving the scope of the invention.

In the context of the present invention, the terms used generically areeach defined as follows:

The term “compound(s) according to the invention” in the context of thecompounds of formulae I, II, III, IV, V, Va, Vb, Vc, VI, VII and VIIIcomprises the compound(s) as defined herein as well as stereoisomers,salts, tautomers or N-oxides thereof. The term “compound(s) of thepresent invention” is to be understood as equivalent to the term“compound(s) according to the invention”.

N-oxides of the compounds of the present invention can only be obtained,if the compounds contain a nitrogen atom, which may be oxidized. This isprincipally the case for the compounds of formulae II, IV, V, Va, Vb,Vc, VI, VII and VIII, but not necessarily the case for compounds offormulae I and III. Accordingly, the term “compound(s) according to theinvention” will only cover stereoisomers, salts and tautomers of thecompounds of formulae I and III, if these compounds do not contain anitrogen substituent, which would allow for the formation of an N-oxide.N-oxides may principally be prepared by standard methods, e.g. by themethod described in Journal of Organometallic Chemistry 1989, 370,17-31. However, it is preferred according to the invention that theintermediate compounds I, II, III and IV in the preparation of thecompounds of formula V are not present in the form of the N-oxides.Furthermore, if it is desired to convert compounds of formula Va or Vbinto compounds of formula Vc, or to convert compounds of formula Vc intocompounds of formula VI, or to convert compounds of formula VI intocompounds of formula VIII, it is also preferred that the compounds arenot present in the form of N-oxides. On the other hand, under certainreaction conditions, it cannot be avoided that N-oxides are formed atleast intermediary.

Stereoisomers of the compounds of formulae I, II, III, IV, V, Va, Vb,Vc, VI, VII and VIII will be present, if the compounds contain one ormore centers of chirality in the substituents. In this case, thecompounds will be present in the form of different enantiomers ordiastereomers, if more than one center of chirality is present. Thecompounds of the present invention cover every possible stereoisomer,i.e. single enantiomers or diastereomers, as well as mixtures thereof.With regard to the compounds of formula V, it is noted that a center ofchirality is also present in the generic formula, if the substituentsR⁴, R⁵ and R⁶ are different from each other. Said center of chirality isnewly formed, when the compounds of formula V are prepared from thecompounds of formula IV. In particular, the sp²-hybridized carbon atom,to which the substituents R⁴ and R⁵ are attached in the compounds offormula IV, may be attacked by the reagent comprising the R⁶ group fromtwo sides, so that principally two configurations can be obtained at theresulting sp³-hybridized carbon atom. The two possible stereoisomers ofthe compounds of formula V, V:SI-A and V:SI-B, which can be obtainedaccording to the process according to the present invention, aredepicted below.

Analogous stereoisomers are also possible for the compounds of formulaVa, Vb, Vc, VI and VIII. Thus, if the substituents R⁴, R⁵ and R⁶ aredifferent from each other, so that a center of chirality is present, thegeneric formulae V, Va, Vb, Vc, VI and VIII as used herein are in eachcase intended to cover two stereoisomers analogous to the twostereoisomers as depicted above. For reasons of clarity, it is notdistinguished between the two stereoisomers of the generic formulae V,Va, Vb, Vc, VI and VIII throughout the specification. Instead the—CR⁴R⁵R⁶ group is depicted without any indication regarding the threedimensional structure, but it is to be understood that the genericformulae V, Va, Vb, Vc, VI and VIII in each case embrace both possiblestereoisomers, if the —CR⁴R⁵R⁶ group is chiral due to different meaningsof R⁴, R⁵ and R⁶.

Geometric isomers of the compounds of the present invention are usuallypossible, if the compounds contain at least one carbon-carbon orcarbon-nitrogen double bond because E- and Z-isomers of the compoundsmay then be present. The compounds of the present invention cover everypossible geometric isomer, i.e. single E- or Z-isomers as well asmixtures thereof. With regard to the compounds of formulae II, III andIV, it is noted that a carbon-carbon double bond and/or acarbon-nitrogen double bond is already present in the generic formula.As in each case the E- and Z-isomers are both intended to be covered,the generic formulae are depicted with wavy lines to the substituents,which indicates that the two substituents at one sp²-hybridized carbonatom may be present in each position. The possible E- and Z-isomers forthe compounds of formula II (i.e. (II:GI-A¹) and II:GI-B¹), III III(i.e. III: GI-A² and III:GI-B²) and IV (i.e. IV:GI-A¹A², IV:GI-B¹A²,IV:GI-A¹B² and IV:GI-B¹B²) are depicted below.

Thus, if E- and Z-isomers are possible, the generic formulae II, III andIV as used herein are in each case intended to cover all geometricisomers as depicted above, which is indicated by the wavy lines to thesubstituents in the generic formulae.

Tautomers of the compounds of formulae I, II, III, IV, V, Va, Vb, Vc,VI, VII and VIII include keto-enol tautomers, imine-enamine tautomers,amide-imidic acid tautomers and the like. Such tautomerism is possible,e.g., for the generic formulae I, II, III, IV and VIII (if R^(1N) is H).Depending on the substituents, which are defined for the compounds offormulae I, II, III, IV, V, Va, Vb, Vc, VI, VII and VIII, furthertautomers may be formed. The compounds of the present invention coverevery possible tautomer.

Depending on the acidity or basicity as well as the reaction conditions,the compounds of formulae I, II, III, IV, V, Va, Vb, Vc, VI, VII andVIII may be present in the form of salts. Such salts will typically beobtained by reacting the compound with an acid, if the compound has abasic functionality such as an amine, or by reacting the compounds witha base, if the compound as an acidic functionality such as a carboxylicacid group. For example, the compounds of formula Vb include 4-pyrazolecarboxylic acid salts, wherein the cation stems from the base, withwhich the 4-pyrazole carboxylic acid has been reacted to give an anioniccarboxylate. If a carboxylic acid group COOH is present in the form of acarboxylate, said anion may be referred to as [C(O)O]⁻, wherein thenegative charge is typically delocalized over the two oxygen atoms ofthe carboxylate group. On the other hand, the cationic charge of anammonium cation, which may be formed from an amino group in the presenceof an acid, is typically not delocalized.

Cations, which stem from a base, with which the compounds of the presentinvention are reacted, are e.g. alkali metal cations M_(a) ⁺, alkalineearth metal cations M_(ea) ²⁺ or ammonium cations NR₄ ⁺, wherein thealkali metals are preferably sodium, potassium or lithium and thealkaline earth metal cations are preferably magnesium or calcium, andwherein the substituents R of the ammonium cation NR₄ ⁺ are preferablyindependently selected from H, C₁-C₁₀-alkyl, phenyl andphenyl-C₁-C₂-alkyl.

Anions, which stem from an acid, with which the compounds of the presentinvention have been reacted, are e.g. chloride, bromide, fluoride,hydrogensulfate, sulfate, dihydrogen-phosphate, hydrogenphosphate,phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate,hexafluorophosphate, benzoate, and the anions of C₁-C₄-alkanoic acids,preferably formate, acetate, propionate and butyrate.

The compounds of the invention may be in the form of solids or liquids.If the compounds are present as solids, the compounds may be amorphousor may exist in one or more different crystalline forms. The compoundsof the present invention cover mixtures of different crystalline formsof the respective compounds as well as amorphous or crystalline saltsthereof.

The organic moieties mentioned in the above definitions of the variablesare—like the term halogen—collective terms for individual listings ofthe individual group members. The prefix C_(n)-C_(m) indicates in eachcase the possible number of carbon atoms in the group.

The term “halogen” denotes in each case fluorine, bromine, chlorine oriodine, in particular fluorine, chlorine or bromine.

The term “alkyl” as used herein and in the alkyl moieties of alkylamino,alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyldenotes in each case a straight-chain or branched alkyl group havingusually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms, more preferably from 1 to 3 carbonatoms. Examples of an alkyl group are methyl, ethyl, n-propyl,iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl,2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl,1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl.

The term “haloalkyl” as used herein and in the haloalkyl moieties ofhaloalkylcarbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl,haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each casea straight-chain or branched alkyl group having usually from 1 to 10carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to4 carbon atoms, wherein the hydrogen atoms of this group are partiallyor totally replaced with halogen atoms. Preferred haloalkyl moieties areselected from C₁-C₄-haloalkyl, more preferably from C₁-C₃-haloalkyl orC₁-C₂-haloalkyl, in particular from C₁-C₂-fluoroalkyl such asfluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,pentafluoroethyl, and the like.

The term “alkoxy” as used herein denotes in each case a straight-chainor branched alkyl group which is bonded via an oxygen atom and hasusually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms. Examples of an alkoxy group are methoxy,ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy,tert.-butyloxy, and the like.

The term “alkoxyalkyl” as used herein refers to alkyl usually comprising1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1carbon atom is substituted by an alkoxy radical usually comprising 1 to4, preferably 1 or 2 carbon atoms as defined above. Examples areCH₂OCH₃, CH₂—OC₂H₅, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.

The term “haloalkoxy” as used herein denotes in each case astraight-chain or branched alkoxy group having from 1 to 10 carbonatoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbonatoms, wherein the hydrogen atoms of this group are partially or totallyreplaced with halogen atoms, in particular fluorine atoms. Preferredhaloalkoxy moieties include C₁-C₄-haloalkoxy, in particularC₁-C₂-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy,trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy,2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,2-chloro-2,2-difluoro-ethoxy, 2,2-dichloro-2-fluoroethoxy,2,2,2-trichloroethoxy, pentafluoroethoxy and the like.

The term “alkylthio “(alkylsulfanyl: alkyl-S—)” as used herein refers toa straight-chain or branched saturated alkyl group having 1 to 10 carbonatoms, preferably 1 to 4 carbon atoms (═C₁-C₄-alkylthio), morepreferably 1 to 3 carbon atoms, which is attached via a sulfur atom.

The term “haloalkylthio” as used herein refers to an alkylthio group asmentioned above wherein the hydrogen atoms are partially or fullysubstituted by fluorine, chlorine, bromine and/or iodine.

The term “alkylsulfinyl” (alkylsulfonyl: C₁-C₆-alkyl-S(═O)—), as usedherein refers to a straight-chain or branched saturated alkyl group (asmentioned above) having 1 to 10 carbon atoms, preferably 1 to 4 carbonatoms (═C₁-C₄-alkylsulfinyl), more preferably 1 to 3 carbon atoms bondedthrough the sulfur atom of the sulfinyl group at any position in thealkyl group.

The term “haloalkylsulfinyl” as used herein refers to an alkylsulfinylgroup as mentioned above wherein the hydrogen atoms are partially orfully substituted by fluorine, chlorine, bromine and/or iodine.

The term “alkylsulfonyl” (alkyl-S(═O)₂—) as used herein refers to astraight-chain or branched saturated alkyl group having 1 to 10 carbonatoms, preferably 1 to 4 carbon atoms (═C₁-C₄-alkylsulfonyl), preferably1 to 3 carbon atoms, which is bonded via the sulfur atom of the sulfonylgroup at any position in the alkyl group.

The term “haloalkylsulfonyl” as used herein refers to an alkylsulfonylgroup as mentioned above wherein the hydrogen atoms are partially orfully substituted by fluorine, chlorine, bromine and/or iodine.

The term “alkylcarbonyl” refers to an alkyl group as defined above,which is bonded via the carbon atom of a carbonyl group (C═O) to theremainder of the molecule.

The term “haloalkylcarbonyl” refers to an alkylcarbonyl group asmentioned above, wherein the hydrogen atoms are partially or fullysubstituted by fluorine, chlorine, bromine and/or iodine.

The term “alkoxycarbonyl” refers to an alkylcarbonyl group as definedabove, which is bonded via an oxygen atom to the remainder of themolecule.

The term “haloalkoxycarbonyl” refers to an alkoxycarbonyl group asmentioned above, wherein the hydrogen atoms are partially or fullysubstituted by fluorine, chlorine, bromine and/or iodine.

The term “alkenyl” as used herein denotes in each case a singlyunsaturated hydrocarbon radical having usually 2 to 10, frequently 2 to6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2-propen-1-yl),1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl),2-buten-1-yl, 3-buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl,1-methylbut-2-en-1-yl, 2-ethylprop-2-en-1-yl and the like.

The term “haloalkenyl” as used herein refers to an alkenyl group asdefined above, wherein the hydrogen atoms are partially or totallyreplaced with halogen atoms.

The term “alkynyl” as used herein denotes in each case a singlyunsaturated hydrocarbon radical having usually 2 to 10, frequently 2 to6, preferably 2 to 4 carbon atoms, e.g. ethynyl, propargyl(2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl,3-butyn-1-yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl,1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like.

The term “haloalkynyl” as used herein refers to an alkynyl group asdefined above, wherein the hydrogen atoms are partially or totallyreplaced with halogen atoms.

The term “cycloalkyl” as used herein and in the cycloalkyl moieties ofcycloalkoxy and cycloalkylthio denotes in each case a monocycliccycloaliphatic radical having usually from from 3 to 10 or from 3 to 6carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl,cyclobutyl, cyclopentyl and cyclohexyl.

The term “halocycloalkyl” as used herein and in the halocycloalkylmoieties of halocycloalkoxy and halocycloalkylthio denotes in each casea monocyclic cycloaliphatic radical having usually from 3 to 10 C atomsor 3 to 6 C atoms, wherein at least one, e.g. 1, 2, 3, 4, or 5 of thehydrogen atoms, are replaced by halogen, in particular by fluorine orchlorine. Examples are 1- and 2-fluorocyclopropyl, 1,2-, 2,2- and2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl,2,2,3,3-tetrafluorocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2-and 2,3-dichlorocyclopropyl, 1,2,2-trichlorocyclopropyl,2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1,2-,2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and3-chlorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-,2,5-dichlorocyclopentyl and the like.

The term “cycloalkoxy” refers to a cycloalkyl group as defined above,which is bonded via an oxygen atom to the remainder of the molecule.

The term “halocycloalkoxy” refers to a halocycloalkyl group as definedabove, which is bonded via an oxygen atom to the remainder of themolecule.

The term “cycloalkylthio” refers to a cycloalkyl group as defined above,which is bonded via a sulfur atom to the remainder of the molecule.

The term “halocycloalkylthio” refers to a halocycloalkyl group asdefined above, which is bonded via a sulfur atom to the remainder of themolecule.

The term “cycloalkylalkyl” refers to a cycloalkyl group as defined abovewhich is bonded via an alkyl group, such as a C₁-C₅-alkyl group or aC₁-C₄-alkyl group, in particular a methyl group (=cycloalkylmethyl), tothe remainder of the molecule.

The term “cycloalkenyl” as used herein and in the cycloalkenyl moietiesof cycloalkenyloxy and cycloalkenylthio denotes in each case amonocyclic singly unsaturated non-aromatic radical having usually from 3to 10, e.g. 3, or 4 or from 5 to 10 carbon atoms, preferably from 3- to8 carbon atoms. Exemplary cycloalkenyl groups include cyclopropenyl,cycloheptenyl or cyclooctenyl.

The term “halocycloalkenyl” as used herein and in the halocycloalkenylmoieties of halocycloalkenyloxy and halocycloalkenylthio denotes in eachcase a monocyclic singly unsaturated non-aromatic radical having usuallyfrom 3 to 10, e.g. 3, or 4 or from 5 to 10 carbon atoms, preferably from3- to 8 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4, or 5 of thehydrogen atoms, are replaced by halogen, in particular by fluorine orchlorine. Examples are 3,3-difluorocyclopropen-1-yl and3,3-dichlorocyclopropen-1-yl.

The term “cycloalkenyloxy” refers to a cycloalkenyl group as definedabove, which is bonded via an oxygen atom to the remainder of themolecule.

The term “halocycloalkenyloxy” refers to a halocycloalkenyl group asdefined above, which is bonded via an oxygen atom to the remainder ofthe molecule.

The term “cycloalkenylthio” refers to a cycloalkenyl group as definedabove, which is bonded via a sulfur atom to the remainder of themolecule.

The term “halocycloalkenylthio” refers to a halocycloalkenyl group asdefined above, which is bonded via a sulfur atom to the remainder of themolecule.

The term “cycloalkenylalkyl” refers to a cycloalkenyl group as definedabove which is bonded via an alkyl group, such as a C₁-C₅-alkyl group ora C₁-C₄-alkyl group, in particular a methyl group (=cycloalkenylmethyl),to the remainder of the molecule.

The term “carbocycle” or “carbocyclyl” includes in general a 3- to12-membered, preferably a 3- to 8-membered or a 5- to 8-membered, morepreferably a 5- or 6-membered monocyclic, non-aromatic ring comprising 3to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms.Preferably, the term “carbocycle” covers cycloalkyl and cycloalkenylgroups as defined above.

The term “heterocycloalkyl” includes in general 3- to 8-membered, inparticular 6-membered monocyclic saturated heterocyclic non-aromaticradicals. The heterocyclic non-aromatic radicals usually comprise 1, 2,or 3 heteroatoms selected from N, O and S as ring members, where S-atomsas ring members may be present as S, SO or SO₂.

The term “heterocycloalkenyl” includes in general 3- to 8-membered, inparticular 6-membered monocyclic singly unsaturated heterocyclicnon-aromatic radicals. The heterocyclic non-aromatic radicals usuallycomprise 1, 2, or 3 heteroatoms selected from N, O and S as ringmembers, where S-atoms as ring members may be present as S, SO or SO₂.

The term “heterocycle” or “heterocyclyl” includes in general 3- to12-membered, preferably 3- to 8-membered or 5- to 8-membered, morepreferably 5- or 6-membered, in particular 6-membered monocyclicheterocyclic non-aromatic radicals. The heterocyclic non-aromaticradicals usually comprise 1, 2, 3, 4, or 5, preferably 1, 2 or 3heteroatoms selected from N, O and S as ring members, where S-atoms asring members may be present as S, SO or SO₂. Examples of 5- or6-membered heterocyclic radicals comprise saturated or unsaturated,non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl,thietanyl-S-oxid (S-oxothietanyl), thietanyl-S-dioxid(S-dioxothiethanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl,tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl,S-oxothiolanyl, S-dioxothiolanyl, dihydrothienyl, S-oxodihydrothienyl,S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thiazolinyl,oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl,tetrahydropyranyl, 1,3- and 1,4-dioxanyl, thiopyranyl, S.oxothiopyranyl,S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl,S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl,S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl,thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, thiazinyland the like. Examples for heterocyclic ring also comprising 1 or 2carbonyl groups as ring members comprise pyrrolidin-2-onyl,pyrrolidin-2,5-dionyl, imidazolidin-2-onyl, oxazolidin-2-onyl,thiazolidin-2-onyl and the like.

The term “aryl” includes mono-, bi- or tricyclic aromatic radicalshaving usually from 6 to 14, preferably 6, 10, or 14 carbon atoms.Exemplary aryl groups include phenyl, naphthyl and anthracenyl. Phenylis preferred as aryl group.

The term “hetaryl” includes monocyclic 5- or 6-membered heteroaromaticradicals comprising as ring members 1, 2, 3, or 4 heteroatoms selectedfrom N, O and S. Examples of 5- or 6-membered heteroaromatic radicalsinclude pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4-, or5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or 4-pyridazinyl,thienyl, i.e. 2- or 3-thienyl, furyl, i.e. 2- or 3-furyl, pyrrolyl, i.e.2- or 3-pyrrolyl, oxazolyl, i.e. 2-, 3-, or 5-oxazolyl, isoxazolyl, i.e.3-, 4-, or 5-isoxazolyl, thiazolyl, i.e. 2-, 3- or 5-thiazolyl,isothiazolyl, i.e. 3-, 4-, or 5-isothiazolyl, pyrazolyl, i.e. 1-, 3-,4-, or 5-pyrazolyl, i.e. 1-, 2-, 4-, or 5-imidazolyl, oxadiazolyl, e.g.2- or 5-[1,3,4]oxadiazolyl, 4- or 5-(1,2,3-oxadiazol)yl, 3- or5-(1,2,4-oxadiazol)yl, 2- or 5-(1,3,4-thiadiazol)yl, thiadiazolyl, e.g.2- or 5-(1,3,4-thiadiazol)yl, 4- or 5-(1,2,3-thiadiazol)yl, 3- or5-(1,2,4-thiadiazol)yl, triazolyl, e.g. 1H-, 2H- or3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H-, 2H-, or 4H-1,2,4-triazolyland tetrazolyl, i.e. 1H- or 2H-tetrazolyl. The term “hetaryl” alsoincludes bicyclic 8 to 10-membered heteroaromatic radicals comprising asring members 1, 2 or 3 heteroatoms selected from N, O and S, wherein a5- or 6-membered heteroaromatic ring is fused to a phenyl ring or to a5- or 6-membered heteroaromatic radical. Examples of a 5- or 6-memberedheteroaromatic ring fused to a phenyl ring or to a 5- or 6-memberedheteroaromatic radical include benzofuranyl, benzothienyl, indolyl,indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl,benzothiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl,1,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyland the like. These fused hetaryl radicals may be bonded to theremainder of the molecule via any ring atom of 5- or 6-memberedheteroaromatic ring or via a carbon atom of the fused phenyl moiety.

The terms “heterocyclyloxy”, “hetaryloxy”, “aryloxy” and “phenoxy” referto heterocyclyl, hetaryl and aryl as defined above and phenyl, which arebonded via an oxygen atom to the remainder of the molecule.

The terms “heterocyclylsulfonyl”, “hetarylsulfonyl”, “arylsulfonyl”, and“phenylsulfonyl” refer to heterocyclyl, hetaryl and aryl as definedabove, and phenyl, respectively, which are bonded via the sulfur atom ofa sulfonyl group to the remainder of the molecule.

The terms “heterocyclylcarbonyl”, “hetarylcarbonyl”, “arylcarbonyl”, and“phenylcarbonyl” refer to heterocyclyl, hetaryl and aryl as definedabove, and phenyl, respectively, which are bonded via the carbon atom ofa carbonyl group (C═O) to the remainder of the molecule.

The terms “heterocyclylalkyl” and “hetarylalkyl” refer to heterocyclylor hetaryl, respectively, as defined above which are bonded via aC₁-C₅-alkyl group or a C₁-C₄-alkyl group, in particular a methyl group(=heterocyclylmethyl or hetarylmethyl, respectively), to the remainderof the molecule.

The terms “arylalkyl” and “phenylalkyl” refer to aryl as defined aboveand phenyl, respectively, which are bonded via C₁-C₅-alkyl group or aC₁-C₄-alkyl group, in particular a methyl group (=arylmethyl orphenylmethyl), to the remainder of the molecule, examples includingbenzyl, 1-phenylethyl, 2-phenylethyl, etc.

The term “arylalkoxy” and “benzyloxy” refer to arylalkyl as definedabove and phenyl-C₁-alkyl, respectively, which are bonded via an oxygenatom, to the remainder of the molecule.

The terms “alkylene”, “cycloalkylene”, “heterocycloalkylene”,“alkenylene”, “cycloalkenylene”, “heterocycloalkenylene” and“alkynylene” refer to alkyl, cycloalkyl, heterocycloalkyl, alkenyl,cycloalkenyl, heterocycloalkenyl and alkynyl as defined above,respectively, which are bonded to the remainder of the molecule, via twoatoms, preferably via two carbon atoms, of the respective group, so thatthey represent a linker between two moieties of the molecule.

The term “cyclic moiety” can refer to any cyclic groups, which arepresent in the compounds of the present invention, and which are definedabove, e.g. cycloalkyl, cycloalkenyl, carbocycle, heterocycloalkyl,heterocycloalkenyl, heterocycle, aryl, hetaryl and the like.

The remarks made below concerning preferred embodiments of the variablesof the compounds of formulae I, II, III, IV, V, Va, Vb, Vc, VI, VII andVIII, and their subvariants are valid on their own as well as preferablyin combination with each other as well as concerning the processes andthe compounds according to the invention.

As already indicated above, the present invention relates in oneembodiment to a process for preparing a pyrazole compound of formula Vcomprising the step of cyclizing a hydrazone substituted α,β-unsaturatedcarbonyl compound of formula IV by reacting it with a reagent comprisinga R⁶ group. Preferred embodiments of the invention relate to thepreparation of the compounds of formula IV and to further conversions ofspecific compounds falling under the generic formula V, in particularVa, Vb, and Vc.

In view of the fact that the compounds of formula V of the presentinvention can be obtained according to the sequence comprising the steps(a) I→II, (b) II+III→IV, and (c) IV→V as described above and hereinafter, and in view of the fact that the compounds of formula V, ifprovided e.g. as compounds of formula Va and Vb, may be furtherconverted according to the sequence comprising the steps (d) Va orVb→Vc, (e) Vc→VI, and (f) VI+VII→VIII as described above and hereinafter, the substituents, which are preferred for the compounds offormula V will also be preferred for its precursors I, II, III and IV,provided that the substituents are present, and the same substituentswill also be preferred for the compounds, which are obtainable from thecompounds of formula Va, Vb and Vc, i.e. the compounds of formula VI andVIII, provided that the substituents are present.

The substituent R¹ is present in the 4-position of the pyrazole ring ofthe compounds of formula V. The substituent R¹ is also present in theprecursors III and IV of the compounds of formula V.

In a preferred embodiment of the invention, R¹ is

H, halogen, CN, NO₂, C₁-C₁₀-alkyl, which may be unsubstituted, may bepartially or fully halogenated, or may be substituted by 1, 2 or 3identical or different substituents R^(x),

C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y¹R^(d), C₃-C₁₂-cycloalkyl, aryl, orhetaryl, wherein the cyclic moieties may be unsubstituted or may besubstituted by 1, 2, 3, 4, or 5 identical or different substituentsselected from the radicals R^(y) and R^(x);

wherein R^(c) is H, C₁-C₄-alkyl or aryl-C₁-C₄-alkyl, or wherein R^(c)together with the C(Y)O group forms a salt [C(Y)O]⁻NH₄ ⁺, [C(Y)O]⁻M_(a)⁺ or [C(Y)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali metal and M_(ea) isan alkaline earth metal;

wherein R^(d) is C₁-C₄-alkyl, C₃-C₆-cycloalkyl, aryl or hetaryl;

wherein Y is O; and

wherein Y¹ is O or NR^(1a), wherein R^(1a) is C₁-C₄-alkyl,C₃-C₆-cycloalkyl, aryl or hetaryl.

In a more preferred embodiment of the invention, R¹ is CN or C(Y)OR^(c),wherein Y is O and R^(c) is C₁-C₄-alkyl or benzyl, preferably ethyl ortert-butyl.

Compounds of formula V, wherein R¹ is C(Y)OR^(c) with Y being O andR^(c) being C₁-C₄-alkyl or aryl-C₁-C₄-alkyl, or wherein R^(c) togetherwith the C(O)O group forms a salt [C(O)O]NR₄ ⁺, [C(O)O]⁻M_(a) ⁺ or[C(O)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali metal and M_(ea) is analkaline earth metal; and wherein the substituents R at the nitrogenatom are independently of each other selected from H, C₁-C₁₀-alkyl,phenyl and phenyl-C₁-C₄-alkyl, are referred to as compounds of formulaVa.

Compounds of formula V, which correspond to compounds of formula Va, arepreferred according to the present invention. The compounds of formulaVa may be directly obtained from the compounds of formula IV accordingto the process of the invention, and they can easily be converted intothe compounds of formula Vc to prepare compounds of formula VIII via theactivated compounds of formula VI.

In a particular preferred embodiment of the invention, the compound offormula V is a compound of formula Va, wherein R^(c) is C₁-C₄-alkyl oraryl-C₁-C₄-alkyl, preferably C₁-C₄-alkyl or benzyl.

Compounds of formula V, wherein R¹ is CN, are referred to as compoundsof formula Vb.

Compounds of formula V, which correspond to compounds of formula Vb, arepreferred according to the present invention. The compounds of formulaVb may be directly obtained from the compounds of formula IV accordingto the process of the invention, and they can easily be converted intothe compounds of formula Vc to prepare compounds of formula VIII via theactivated compounds of formula VI.

Compounds of formula V, wherein R¹ is C(Y)OR^(c) with Y being O andR^(c) being H, are referred to as compounds of formula Vc.

Compounds of formula V, which correspond to compounds of formula Vc, arepreferred according to the present invention. In certain situations, thecompounds of formula Vc may be directly obtained from the compounds offormula IV according to the process of the invention. However, it can bepreferred to perform the cyclization of the compounds of formula IV withthe carboxylic acid group being masked as an ester or a nitrile group.Thus, the compounds of formula Vc are may also be obtained from thecompounds of formula Va or Vb as described above. The compounds offormula Vc then represent versatile reaction tools for the preparationof 4-pyrazole N-(het)arylamide compounds of formula VIII, as they caneasily be activated for a subsequent amidation reaction to give the4-pyrazole N-(het)arylamide compounds of formula VIII.

The substituent R² is present in the 5-position of the pyrazole ring ofthe compounds of formulae V, Va, Vb, Vc, VI and VIII. Furthermore, thesubstituent R² is present in the precursors III and IV of the compoundsof formula V.

In a preferred embodiment of the invention R² is

C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fullyhalogenated, or may be substituted by 1, 2 or 3 identical or differentsubstituents R^(x),

C₃-C₁₂-cycloalkyl, aryl, or hetaryl, wherein the three last mentionedradicals may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5identical or different substituents selected from the radicals R^(y) andR^(x).

In a more preferred embodiment of the invention, R² is C₁-C₄-alkyl,which may be unsubstituted, or may be partially or fully halogenated.

It is even more preferred that R² is CH₃, CH₂CH₃ or fluoromethyl, andparticularly preferred that R² is CH₃, CF₂H or CF₃.

The substituent R³ is present in the 3-position of the pyrazole ring ofthe compounds of formulae V, Va, Vb, Vc, VI and VIII. Furthermore, thesubstituent R³ is present in the precursors III and IV of the compoundsof formula V.

In a preferred embodiment of the invention R² is

-   -   H, C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or        fully halogenated, or may be substituted by 1, 2 or 3 identical        or different substituents R^(x),    -   C₃-C₁₂-cycloalkyl, aryl, or hetaryl, wherein the cyclic moieties        may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5        identical or different substituents selected from the radicals        R^(y) and R^(x).

In a more preferred embodiment of the invention, R³ is H.

As already indicated above, the process according to the presentinvention is particularly advantageous for regioselectively preparingN-substituted pyrazole compounds, which are 3- or 5-substituted orsubstituted with different substituents in the 3- and 5-position. Thus,compounds of formula V, wherein R³ and R² are different from each otherare particularly preferred. It is particularly preferred that one of R³and R² is H and the other one is different from H. Alternatively, it canbe preferred that R³ and R² are both different from H, and differentfrom each other.

Compounds of formula V, wherein R³ is different from H and wherein R² isH, are to be understood as 3-substituted N-substituted pyrazolecompounds and are referred to as compounds of formula V.3-R³_(subst).5-H, wherein R³ _(subst) refers to a substituent defined forR³, which is other than H.

Compounds of formula V, wherein R³ is H and wherein R² is different fromH, are to be understood as 5-substituted N-substituted pyrazolecompounds and are referred to as compounds of formula V.3-H.5-R²_(subst), wherein R² _(subst) refers to a substituent defined for R²,which is other than H.

Compounds of formula V, wherein R³ and R² are different from H anddifferent from each other, are to be understood as 3- and 5-substitutedN-substituted pyrazole compounds, wherein the substituents in the 3- and5-position are different from each other. Such compounds are referred toas compounds of formula V.3-R³ _(subst).5-R² _(subst), wherein R³_(subst) refers to a substituent defined for R³, which is other than H,and wherein R² _(subst) refers to a substituent defined for R², which isother than H, with the proviso that R³ _(subst) and R² _(subst) aredifferent from each other. The compounds are depicted below.

The meanings for R² and R³, i.e. that one of R³ and R² is H and theother one is different from H, or that R³ and R² are both different fromH, and different from each other, are also preferred for the precursorsIII and IV as well as for the compounds of formulae Va, Vb, Vc, VI andVIII.

Compounds of formula V.3-H.5-R² _(subst) and analogously substitutedcompounds of formulae III, IV, Va, Vb, Vc, VI and VIII are particularlypreferred according to the present invention.

The substituents R⁴ and R⁵ are present in the compounds of formulae I,II, IV, V, Va, Vb, Vc, VI and VIII.

In one preferred embodiment of the invention,

-   -   R⁴ is selected from C₁-C₁₀-alkyl, which may be unsubstituted,        may be partially or fully halogenated, or may be substituted by        1, 2 or 3 identical or different substituents R^(x), and        C₃-C₁₀-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2, 3, 4, or 5 identical or different        substituents R^(y); and    -   R⁵ is selected from C₁-C₁₀-alkyl, which may be unsubstituted,        may be partially or fully halogenated, or may be substituted by        1, 2 or 3 identical or different substituents R^(x), and        C₃-C₁₀-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2, 3, 4, or 5 identical or different        substituents R^(y).

In a more preferred embodiment of this embodiment,

-   -   R⁴ is selected from C₁-C₄-alkyl, which may be unsubstituted, may        be partially or fully halogenated, or may be substituted by 1 or        2 identical or different substituents R^(x), wherein R^(x) is        selected from CN and C(O)NH₂, and    -   C₃-C₆-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2 or 3 identical or different substituents        R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂;        and    -   R⁵ is selected from C₁-C₄-alkyl, which may be unsubstituted, may        be partially or fully halogenated, or may be substituted by 1 or        2 identical or different substituents R^(x), wherein R^(x) is        selected from CN and C(O)NH₂, and    -   C₃-C₆-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2 or 3 identical or different substituents        R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂.

In an even more preferred embodiment of this embodiment,

-   -   R⁴ is selected from C₁-C₄-alkyl, which may be unsubstituted, may        be partially or fully halogenated, or may be substituted by 1 or        2 identical or different substituents R^(x), wherein R^(x) is        selected from CN and C(O)NH₂, and    -   C₃-C₆-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2 or 3 identical or different substituents        R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂;        and    -   R⁵ is selected from C₁-C₂-alkyl, which may be unsubstituted, may        be partially or fully halogenated, or may be substituted by 1 or        2 identical or different substituents R^(x), wherein R^(x) is        selected from CN and C(O)NH₂, and    -   C₃-C₄-cycloalkyl, which may be unsubstituted or may be        substituted by 1, 2 or 3 identical or different substituents        R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂.

It is particularly preferred according to this embodiment of the presentinvention that R⁴ and R⁵ are different from each other. For example, R⁵may be C₁-C₂-alkyl, which is unsubstituted, or C₃-C₄-cycloalkyl, whichis unsubstituted, while R⁴ may be C₁-C₄-alkyl, which may beunsubstituted, or partially or fully halogenated, or substituted with 1or 2 identical or different substituents R^(x) selected from CN andC(O)NH₂, or may be C₃-C₆-cycloalkyl, which may preferably be substitutedwith 1, 2 or 3 identical or different substituents R^(y) selected fromhalogen, CN and C(O)NH₂.

Most preferably, R⁵ is CH₃, while R⁴ is C₁-C₄-alkyl, C₁-C₂-haloalkyl, orC₃-cycloalkyl, wherein the cycloalkyl group is preferably substitutedwith one substituent selected from CN and C(O)NH₂. Suitable combinationsof R⁵ and R⁴ may thus e.g. be CH₃/i-Pr or CH₃/1-CN-cC₃H₄.

In another preferred embodiment of the invention,

-   -   R⁴ and R⁵ together with the carbon atom to which they are        attached form a 3- to 12-membered non-aromatic carbocycle, which        may be partially or fully substituted by R^(j).

In a more preferred embodiment of this embodiment,

-   -   R⁴ and R⁵ together with the carbon atom to which they are        attached form a 3- to 12-membered non-aromatic, saturated        carbocycle, which may be partially or fully substituted by        R^(j), wherein R^(j) is selected from halogen, CN and C(O)NH₂.

In an even more preferred embodiment of this embodiment,

-   -   R⁴ and R⁵ together with the carbon atom to which they are        attached form a 3- to 6-membered non-aromatic, saturated        carbocycle, which may be partially or fully substituted by        R^(j), wherein R^(j) is selected from halogen, CN and C(O)NH₂.

It is particularly preferred according to this embodiment of the presentinvention that R⁴ and R⁵ together with the carbon atom to which they areattached form a 6-membered carbocycle, which is partially or fullyhalogenated, preferably fluorinated. Thus, R⁴ and R⁵ may togetherrepresent e.g. —CH₂CH₂CF₂CH₂CH₂—.

The substituent R⁶ is present in the compounds of formulae V, Va, Vb,Vc, VI and VIII and in the reagent, with which the compound of formulaIV is reacted to give the compound of formula V.

In one preferred embodiment of the invention, R⁶ is selected from H, CNand C₁-C₂-fluoroalkyl. More preferably R⁶ is selected from H, CN, CHF₂and CF₃, and most preferably, R⁶ is H.

Compounds of formula V, wherein R⁶ is H may be referred to as compoundsof formula V.R⁶—H.

Compounds of formula V.R⁶—H and analogously substituted compounds offormulae Va, Vb, Vc, VI and VIII are particularly preferred according tothe present invention.

Compounds of formula V.3-H.5-R² _(subst), wherein R⁶ is H, i.e.compounds of formula V.3-H.5-R² _(subst).R⁶—H and analogouslysubstituted compounds of formulae III, IV, Va, Vb, Vc, VI and VIII areparticularly preferred according to the present invention.

As already indicated above, a center of chirality may be formed upon theformation of the compounds of formula V by reacting a compound offormula IV with a reagent comprising a R⁶ group, if the substituents R⁴and R⁵ of the compound of formula IV and R⁶ are different from eachother. If two or more of the three substituents R⁴, R⁵ and R⁶ areidentical, no center of chirality will be formed upon the formation ofthe compounds of formula V. It is particularly preferred according tothe present invention that R⁴, R⁵ and R⁶ are different from each other,so that a center of chirality is formed. If a center of chirality isformed, it is preferred that the two possible configurations of thecenter of chirality are formed in equal amounts. Thus, the formation ofthe compounds of formula V according to the present invention is usuallynot stereoselective, but a mixture, preferably a racemic mixture, of thetwo possible stereoisomers is obtained. If a center of chirality ispresent at the —CR⁴R⁵R⁶ group of the compounds of formula V, genericformula V is therefore preferably intended to cover a mixture of the twopossible stereoisomers. If no further centers of chirality are presentin the compound, the stereoisomers are enantiomers, otherwise thestereoisomers may be diastereoisomers. The same considerations alsoapply for generic formulae Va, Vb, Vc, VI and VIII.

With regard to the reagent comprising the R⁶ group, which is reactedwith the compounds of formula IV to give the compounds of formula V, thefollowing is noted.

For R⁶ being H, it is preferred that the reagent is present in the formof “reagent-R⁶”, and transfers H as a hydride. In certain situations, itcan also be preferred that the reagent transfers H as a hydrogenradical.

In one preferred embodiment of the invention, the reagent comprising Has the R⁶ group is a reducing agent. Preferably, the reducing agents areselected from

-   -   (ia) ionic hydride donors selected from the group consisting of        complex hydrides of boron and aluminum,    -   (ib) non-ionic hydride donors selected from the group consisting        of dihydrogen, which is particularly preferably used in        combination with a metal catalyst, Hantzsch ester,        1,4-dihydrobenzol, isopropanol, formic acid, and ammonium        formate, and    -   (ic) electron donors, which are used in combination with        protons, wherein the electrons are donated by a cathode or a        metal selected from Li, Na, K, Mg, Zn, Fe and Al.

Ionic hydride donors are described in the following and are particularlypreferred according to the present invention.

Although the term “ionic” indicates that the “ionic hydride donors” havean ionic structure, ionic hydride donors principally belong to the groupof reagents, which comprise R⁶, i.e. H, covalently bonded, and may thusbe referred to as “reagent-H”, which may react with compounds of formulaIV. However, an ionic structure is nevertheless present in ionic hydridedonors because the reagent, which comprises H covalently bonded, isitself ionic, preferably anionic, i.e. in the form “[reagent-H]⁻”, sothat the reagent is typically provided in the form of a salt“Ct⁺[reagent-H]⁻”, wherein Ct⁺ represents a cation, e.g. an alkali metalcation, and “[reagent-H]⁻” is as defined above. Preferably, the ionichydride donor is a negatively charged hydrido complex of a metal, whichis provided in the form of a salt and is capable of transferring H as ahydride.

In a particular preferred embodiment of the invention, the ionic hydridedonor is selected from the group consisting of complex hydrides of boronand aluminium.

The term “complex hydride of boron or aluminum” refers to hydridocomplexes of boron or aluminum. Thus, R⁶ being H may be covalentlybonded to a boron or aluminum atom to give a hydrido complex, which iscapable of transferring H as a hydride as indicated above. Preferably,the boron or aluminum complex is negatively charged due to the presenceof four substituents, of which one is H as the group R⁶, which can betransferred in the form of a hydride, and the three remainingsubstituents can independently of each other e.g. be selected from thegroup consisting of H, C₁-C₄-alkyl, C₁-C₄-alkoxy and CN. Thus, thecomplex may be described by the formula “[reagent-H]⁻” defined above.Typically, the anionic hydrido complex of boron or aluminum is combinedwith a cation in the form of a salt, e.g. according to the formula“Ct⁺[reagent-H]⁻” mentioned above. The cation Ct⁺ is typically an alkalimetal ion, which is preferably Na⁺ or Li⁺.

Preferred complex hydrides of boron and aluminum include Na⁺[BH₄]⁻,Na⁺[B(CN)H₃]⁻, Na⁺[BH(OAc)₃]⁻, Li⁺[AlH₄]⁻, Li⁺[AlH(Otert-Bu)₄]⁻,Li⁺[BH₄]⁻, Li⁺[BHEt₃]⁻, Li⁺[BH(sec-Bu)₃]⁻ and the like. Complex hydridesof aluminum are usually preferred, if a high reactivity of the reagentcomprising the R⁶ group is desired. Complex hydrides of boron aretypically milder reducing agents. For the purposes of the presentinvention, complex hydrides of boron are usually preferred. Mostpreferably, the reagent comprising R⁶ is Na⁺[BH₄]⁻ or Na⁺[BCNH₃]⁻,particularly preferably Na⁺[B(CN)H₃]⁻. The reagent Na⁺[B(CN)H₃]⁻ has thefollowing structure.

Typically, Na⁺[B(CN)H₃]⁻ is also referred to as NaB(CN)H₃ or NaBH₃CN.Similarly, also the other complex hydrides of boron and aluminium listedabove are often referred to by a molecular formula without indicatingcharges.

The structures of other complex hydrides of boron and aluminum includingthe ones listed above are analogous.

In the following, non-ionic hydride donors are described.

The term “non-ionic hydride donor” refers to reagents comprising a R⁶group being H, which are non-ionic and typically belong to the group ofreagents, which comprise R⁶, i.e. H, covalently bonded. Preferably, thenon-ionic hydride donor is a non-charged hydrogen source, which iscapable of transferring H in the form of a hydride, and usually alsotransfers a proton, so that a dihydrogen molecule is transferred in theend. If the reagents transfer H in the form of a hydride, they may againbe considered as “reagent-H” as described above.

As used herein, the term “non-ionic hydride donor” also coversdihydrogen because the result of a hydrogenation reaction withdihydrogen may principally also be seen in the transfer of a hydride anda proton. However, such a hydrogenation may of course also take place assuch that two non-charged hydrogen atoms, i.e. hydrogen radicals, aretransferred.

In a particular preferred embodiment of the invention, the reagentcomprising the R⁶ group is a non-ionic hydrogen donor, which is selectedfrom the group consisting of Hantzsch ester, 1,4-dihydrobenzol,isopropanol, formic acid, ammonium formate, and dihydrogen.

Hantzsch ester, 1,4-dihydrobenzol, isopropanol, formic acid, andammonium formate are also known in the art as “transfer hydrogenationreagents”. They can be considered as hydrogen sources as they cantransfer a hydride ion and a proton. Reactions with these transferhydrogenation reagents can typically be carried out metal-free, i.e. inthe absence of a metal catalyst.

The reaction with dihydrogen (H₂) as reducing agent is preferablyperformed in combination with a metal catalyst. A skilled person knowssuitable metal catalysts to be used in combination with dihydrogen.Examples of suitable metal catalysts are provided further below.

In the following, the reductive cyclization, which is performed withprotons in combination with electrons provided by an electrode or by ametal, is described.

The protons are preferably provided by protic solvents, preferably wateror an alcohol such as methanol, ethanol or isopropanol, and theelectrons are generated from an electrode (cathode) or a suitable metal,preferably a metal selected from Li, Na, K, Mg, Fe and Al.

For R⁶ being different from H, the reagent may be present in a form,wherein R⁶ is covalently bonded, i.e. in the form of “reagent-R⁶”, or inthe form of a salt with R⁶ representing the anion, i.e. in the form of“[reagent]⁺[R⁶]⁻”.

In one preferred embodiment of the invention, the reagent comprising theR⁶ group being different from H is an organometallic reagent, wherein R⁶is selected from C₁-C₆-fluoroalkyl, C₁-C₆-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₂-alkyl,C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenyl-C₁-C₂-alkyl, heterocyclyl,heterocyclyl-C₁-C₂-alkyl, aryl, aryl-C₁-C₂-alkyl, hetaryl,hetaryl-C₁-C₂-alkyl, wherein the carbon chains or cyclic moieties may beunsubstituted, partially or fully substituted by identical or differentsubstituents R^(x). Preferably, the reagent comprising the R⁶ group isan organometallic reagent, wherein R⁶ is selected fromC₁-C₄-fluoroalkyl, C₁-C₄-alkyl, aryl, arylmethyl and allyl, and whereinR⁶ is particularly preferably selected from C₁-C₂-fluoroalkyl, inparticular from CH₂F and CF₃.

Preferably, the organometallic reagent comprises a metal M selected fromLi, Mg, Cu, Zn, Si, Mn or In. Depending on the metal, the organometallicreagent may be considered as “reagent-R⁶” (e.g. M-R⁶) or“[reagent]⁺[R⁶]⁻” (e.g. [M]⁺[R⁶]⁻), but should preferably be consideredas “reagent-R⁶” because the above listed metals are known to formcovalent bonds rather than ionic bonds with organic groups as listedabove for R⁶.

Preferred organometallic reagents according to the present inventioninclude Grignard reagents, cuprate reagents, allyl silanes(Hosomi-Sakurai reagents) and fluoroalkyl silanes (e.g. Ruppert'sreagent).

Particularly preferably, the organometallic reagent is Ruppert'sreagent, i.e. trimethyl(trifluoromethyl)silane, which transfers CF₃ as aR⁶ group.

In another preferred embodiment of the invention, the reagent comprisingthe R⁶ group being different from H is a nucleophilic reagent of formulaH—R⁶, M_(a) ⁺R⁶⁻ or ½M_(ea) ²⁺R⁶⁻, wherein M_(a) is an alkaline metaland M_(ae) is an alkaline earth metal, and wherein R⁶ is selected fromCN, OR^(a), SR^(a), NR^(e)R^(f), and groups of the general formula (i)

wherein R^(a), R^(e), R^(f), R^(r), R^(s) and R^(t) are as definedabove.

The wavy line in the groups of the general formula (i) indicated theposition, where the group (i) may be connected to H according to formulaH—R⁶, or may have been deprotonated to give a salt of formula M_(a) ⁺R⁶⁻or ½M_(ea) ²⁺R⁶⁻, If the group (i) is present in deprotonated, i.e.anionic, form, the negative charge may be delocalized over the1,3-di(thio)carbonyl system. It is noted, however, that the carbon atombetween the two (thio)carbonyl groups will nevertheless be thenucleophilic position of the group (i). Preferred groups (i) are1,3-dicarbonyl compounds, which have been deprotonated in the 2-positionwith a suitable base, and are thus present in anionic form in thecombination with a cation, which stems from the base. The reagentcomprising group (i) as group R⁶ may thus preferably be represented bythe formula M_(a) ⁺R⁶⁻ or ½M_(ea) ²⁺R⁶⁻, which may both be considered asfalling under the above formula “[reagent]⁺[R⁶]⁻”, and wherein M_(a) maye.g. be Li, K or Na, and M_(ea) may e.g. be Mg or Ca. It is noted that,if the reagent comprising group (i) as group R⁶ falls under formulaH—R⁶, it may be considered as a “reagent-R⁶” described above with“reagent” being H.

Preferred groups OR^(a) include C₁-C₄-alkoxy and C₃-C₆-cycloalkoxy.

Preferred groups SR^(a) include C₁-C₄-alkylthio andC₃-C₆-cycloalkylthio.

Preferred groups NR^(e)R^(f) include C₁-C₄-alkylamino,C₁-C₄-dialkylamino, wherein the alkyl chains may have an identical ordifferent length, morpholine, piperazine and N-methylpiperazine.

For the group R⁶ being OR^(a), SR^(a) or NR^(e)R^(f), the reagentcomprising the R⁶ group can either be represented by the formula H—R⁶,which can be considered as falling under the above formula “reagent-R⁶”,or by any one of formulae M_(a) ⁺R⁶⁻ and ½M_(ea) ²⁺R⁶⁻,R⁶, which mayboth be considered as falling under the above formula “[reagent]⁺[R⁶]⁻”,and wherein M_(a) may e.g. be Li, K or Na, and M_(ea) may e.g. be Mg orCa. For the reagent comprising OR^(a) or SR^(a) as R⁶ group, it can bepreferred that the reagent is present in the form of M_(a) ⁺R⁶⁻ or½M_(ea) ²⁺R⁶⁻. For the reagent comprising NR^(e)R^(f) as R⁶ group, itcan be preferred that the reagent is present in the form of H—R⁶ becauseH—NR^(e)R^(f) also has a nucleophilic reactivity, if it is used inprotonated form.

For the R⁶ group being CN, similar considerations apply. Thus, thereagent comprising CN as the R⁶ group can either be represented by theformula H—R⁶, which can be considered as falling under the above formula“reagent-R⁶”, or by any one of formulae M_(a) ⁺R⁶⁻ and ½M_(ea) ²⁺R⁶⁻,R⁶,which may both be considered as falling under the above formula“[reagent]⁺[R⁶]⁻”, and wherein M_(a) may e.g. be Li, K or Na, and M_(ea)may e.g. be Mg or Ca. If R⁶ is CN, the reagent comprising the R⁶ groupis preferably HCN, NaCN or KCN.

It is noted that it is particularly preferred for the reagent being anucleophilic reagent comprising the R⁶ group that R⁶ is CN. NaCN is aparticularly preferred reagent comprising a group R⁶.

The following embodiments regarding the reagent comprising a R⁶ groupare preferred according to the present invention.

In one preferred embodiment, the R⁶ group of the reagent comprising theR⁶ group is H, and the reagent comprising the R⁶ group is selected from

-   -   (ia) ionic hydride donors selected from the group consisting of        complex hydrides of boron and aluminum, or    -   (ib) non-ionic hydride donors selected from the group consisting        of dihydrogen, which is preferably used in combination with a        metal catalyst, Hantzsch ester, 1,4-dihydrobenzol, isopropanol,        formic acid, and ammonium formate.

In another preferred embodiment, the R⁶ group of the reagent comprisingthe R⁶ group is H, and the reagent comprising the R⁶ group is selectedfrom

-   -   (ia) ionic hydride donors selected from the group consisting of        complex hydrides of boron and aluminum, or    -   (ib) dihydrogen, which used in combination with a metal        catalyst.

With regard to option (a), the following embodiments are preferred.

In one preferred embodiment, the R⁶ group of the reagent comprising theR⁶ group is H, and the reagent comprising the R⁶ group is an alkali saltof a negatively charged boron or aluminum complex, wherein the boron oraluminum is substituted by four substituents, of which at least one isH, and the three remaining substituents are independently selected fromthe group consisting of H, C₁-C₄-alkyl, C₁-C₄-alkoxy, and CN.

In a more preferred embodiment, the R⁶ group of the reagent comprisingthe R⁶ group is H, and the reagent comprising the R⁶ group is a sodiumsalt of a negatively charged boron complex, wherein the boron issubstituted by four substituents, of which at least one is H, and thethree remaining substituents are independently selected from the groupconsisting of H, C₁-C₄-alkyl, C₁-C₄-alkoxy, and CN.

In a particularly preferred embodiment, the R⁶ group of the reagentcomprising the R⁶ group is H, and the reagent comprising the R⁶ group isNa⁺[B(CN)H₃]⁻.

With regard to option (b), the following embodiments are preferred.

In one preferred embodiment, the R⁶ group of the reagent comprising theR⁶ group is H, and the reagent comprising the R⁶ group is dihydrogen(H₂), which is used in combination with a metal catalyst.

In a more preferred embodiment, the R⁶ group of the reagent comprisingthe R⁶ group is H, and the reagent comprising the R⁶ group isdihydrogen, which is used in combination with a metal catalyst selectedfrom the group consisting of Rayney-Nickel, Pd/C, Pt/C, and PtO₂.

In an even more preferred embodiment, the R⁶ group of the reagentcomprising the R⁶ group is H, and the reagent comprising the R⁶ group isdihydrogen, which is used in combination with a metal catalyst selectedfrom the group consisting of Rayney-Nickel, Pd/C, Pt/C, and PtO₂, andwherein the dihydrogen is applied with a pressure, which does not exceed100 bar, and preferably does not exceed 50 bar.

In an even more preferred embodiment, the R⁶ group of the reagentcomprising the R⁶ group is H, and the reagent comprising the R⁶ group isdihydrogen, which is used in combination with a metal catalyst selectedfrom the group consisting of Rayney-Nickel, Pd/C, Pt/C, and PtO₂, and incombination with a catalytic amount of an acid, and wherein thedihydrogen is applied with a pressure, which does not exceed 100 bar,and preferably does not exceed 50 bar.

In an even more preferred embodiment, the R⁶ group of the reagentcomprising the R⁶ group is H, and the reagent comprising the R⁶ group isdihydrogen, which is used in combination with a metal catalyst selectedfrom the group consisting of Rayney-Nickel, Pd/C, Pt/C, and PtO₂, and incombination with a catalytic amount of an acid, which is selected fromaromatic sulfonic acids such as toluene sulfonic acid; alkylsulfonicacids, such as methyl sulfonic acid; aromatic carboxylic acids such asbenzoic acid; alkylcarboxylic acids such as acetic acid;haloalkylcarboxylic acids such as trifluoroacetic acid, and mineralacids such as hydrogen chloride or sulfuric acid in methanol, andwherein the dihydrogen is applied with a pressure, which does not exceed100 bar, and preferably does not exceed 50 bar.

In an even more preferred embodiment, the R⁶ group of the reagentcomprising the R⁶ group is H, and the reagent comprising the R⁶ group isdihydrogen, which is used in combination with a metal catalyst selectedfrom the group consisting of Rayney-Nickel, Pd/C, Pt/C, and PtO₂, and incombination with a catalytic amount of an acid, which is selected fromHCl, H₂SO₄, and trifluoracetic acid, and wherein the dihydrogen isapplied with a pressure, which does not exceed 100 bar, and preferablydoes not exceed 50 bar.

Summarizing, the reagent comprising the R⁶ group, which is reacted withthe compounds of formula IV to give the compounds of formula V, may be

-   -   a reducing agent, which may preferably be an ionic hydride        donor, and is particularly preferably Na⁺[B(CN)H₃]⁻; or    -   an organometallic reagent, which may preferably be a silane,        such as an allyl silane or a fluoroalkylsilane, and is        particularly preferably Ruppert's reagent; or    -   a nucleophilic reagent, which may preferably be selected from        HCN, or a salt, such as NaCN, or KCN, and is particularly        preferably NaCN.

In summary, the following combinations of substituents are preferred inthe compounds of formula V and its precursors or the reagents used inthe process of the present invention.

Table 1

Combination, in which R¹ is H, R² is CH₃, R³ is H and the combination ofR⁴ and R⁵ corresponds in each case to one row of Table A

Table 2

Combination, in which R¹ is H, R² is CH₃, R³ is C₃H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 3

Combination, in which R¹ is H, R² is CH₃, R³ is C₆H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 4

Combination, in which R¹ is H, R² is C₃H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 5

Combination, in which R¹ is H, R² is C₃H₅, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 6

Combination, in which R¹ is H, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 7

Combination, in which R¹ is H, R² is C₆H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 8

Combination, in which R¹ is H, R² is C₆H₅, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 9

Combination, in which R¹ is H, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 10

Combination, in which R¹ is H, R² is CF₂H, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 11

Combination, in which R¹ is H, R² is CF₂H, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 12

Combination, in which R¹ is H, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 13

Combination, in which R¹ is H, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 14

Combination, in which R¹ is H, R² is CF₃, R³ is H and the combination ofR⁴ and R⁵ corresponds in each case to one row of Table A

Table 15

Combination, in which R¹ is H, R² is CF₃, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 16

Combination, in which R¹ is H, R² is CF₃, R³ is C₃H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 17

Combination, in which R¹ is H, R² is CF₃, R³ is C₆H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 18

Combination, in which R¹ is F, R² is CH₃, R³ is H and the combination ofR⁴ and R⁵ corresponds in each case to one row of Table A

Table 19

Combination, in which R¹ is F, R² is CH₃, R³ is C₃H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 20

Combination, in which R¹ is F, R² is CH₃, R³ is C₆H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 21

Combination, in which R¹ is F, R² is C₃H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 22

Combination, in which R¹ is F, R² is C₃H₅, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 23

Combination, in which R¹ is F, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 24

Combination, in which R¹ is F, R² is C₆H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 25

Combination, in which R¹ is F, R² is C₆H₅, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 26

Combination, in which R¹ is F, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 27

Combination, in which R¹ is F, R² is CF₂H, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 28

Combination, in which R¹ is F, R² is CF₂H, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 29

Combination, in which R¹ is F, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 30

Combination, in which R¹ is F, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 31

Combination, in which R¹ is F, R² is CF₃, R³ is H and the combination ofR⁴ and R⁵ corresponds in each case to one row of Table A

Table 32

Combination, in which R¹ is F, R² is CF₃, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 33

Combination, in which R¹ is F, R² is CF₃, R³ is C₃H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 34

Combination, in which R¹ is F, R² is CF₃, R³ is C₆H₅ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 35

Combination, in which R¹ is CH₃, R² is CH₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 36

Combination, in which R¹ is CH₃, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 37

Combination, in which R¹ is CH₃, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 38

Combination, in which R¹ is CH₃, R² is C₃H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 39

Combination, in which R¹ is CH₃, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 40

Combination, in which R¹ is CH₃, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 41

Combination, in which R¹ is CH₃, R² is C₆H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 42

Combination, in which R¹ is CH₃, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 43

Combination, in which R¹ is CH₃, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 44

Combination, in which R¹ is CH₃, R² is CF₂H, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 45

Combination, in which R¹ is CH₃, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 46

Combination, in which R¹ is CH₃, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 47

Combination, in which R¹ is CH₃, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 48

Combination, in which R¹ is CH₃, R² is CF₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 49

Combination, in which R¹ is CH₃, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 50

Combination, in which R¹ is CH₃, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 51

Combination, in which R¹ is CH₃, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 52

Combination, in which R¹ is C₆H₅, R² is CH₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 53

Combination, in which R¹ is C₆H₅, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 54

Combination, in which R¹ is C₆H₅, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 55

Combination, in which R¹ is C₆H₅, R² is C₃H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 56

Combination, in which R¹ is C₆H₅, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 57

Combination, in which R¹ is C₆H₅, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 58

Combination, in which R¹ is C₆H₅, R² is C₆H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 59

Combination, in which R¹ is C₆H₅, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 60

Combination, in which R¹ is C₆H₅, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 61

Combination, in which R¹ is C₆H₅, R² is CF₂H, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 62

Combination, in which R¹ is C₆H₅, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 63

Combination, in which R¹ is C₆H₅, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 64

Combination, in which R¹ is C₆H₅, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 65

Combination, in which R¹ is C₆H₅, R² is CF₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 66

Combination, in which R¹ is C₆H₅, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 67

Combination, in which R¹ is C₆H₅, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 68

Combination, in which R¹ is C₆H₅, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 69

Combination, in which R¹ is C(O)OCH₃, R² is CH₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 70

Combination, in which R¹ is C(O)OCH₃, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 71

Combination, in which R¹ is C(O)OCH₃, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 72

Combination, in which R¹ is C(O)OCH₃, R² is C₃H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 73

Combination, in which R¹ is C(O)OCH₃, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 74

Combination, in which R¹ is C(O)OCH₃, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 75

Combination, in which R¹ is C(O)OCH₃, R² is C₆H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 76

Combination, in which R¹ is C(O)OCH₃, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 77

Combination, in which R¹ is C(O)OCH₃, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 78

Combination, in which R¹ is C(O)OCH₃, R² is CF₂H, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 79

Combination, in which R¹ is C(O)OCH₃, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 80

Combination, in which R¹ is C(O)OCH₃, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 81

Combination, in which R¹ is C(O)OCH₃, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 82

Combination, in which R¹ is C(O)OCH₃, R² is CF₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 83

Combination, in which R¹ is C(O)OCH₃, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 84

Combination, in which R¹ is C(O)OCH₃, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 85

Combination, in which R¹ is C(O)OCH₃, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 86

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CH₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 87

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 88

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 89

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₃H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 90

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 91

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 92

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₆H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 93

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 94

Combination, in which R¹ is C(O)OCH₂CH₃, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 95

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₂H, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 96

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 97

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 98

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 99

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 100

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 101

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 102

Combination, in which R¹ is C(O)OCH₂CH₃, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 103

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CH₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 104

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 105

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 106

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₃H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 107

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 108

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 109

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₆H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 110

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 111

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 112

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₂H, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 113

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 114

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 115

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 116

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 117

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 118

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 119

Combination, in which R¹ is C(O)OC(CH₃)₃, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 120

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CH₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 121

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 122

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 123

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₃H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 124

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 125

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 126

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₆H₅, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 127

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 128

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 129

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₂H, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 130

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 131

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 132

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 133

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₃, R³ is H and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 134

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₃, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 135

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 136

Combination, in which R¹ is C(O)OCH₂C₆H₅, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 137

Combination, in which R¹ is CN, R² is CH₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 138

Combination, in which R¹ is CN, R² is CH₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 139

Combination, in which R¹ is CN, R² is CH₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 140

Combination, in which R¹ is CN, R² is C₃H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 141

Combination, in which R¹ is CN, R² is C₃H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 142

Combination, in which R¹ is CN, R² is C₃H₅, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 143

Combination, in which R¹ is CN, R² is C₆H₅, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 144

Combination, in which R¹ is CN, R² is C₆H₅, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 145

Combination, in which R¹ is CN, R² is C₆H₅, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 146

Combination, in which R¹ is CN, R² is CF₂H, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 147

Combination, in which R¹ is CN, R² is CF₂H, R³ is CH₃ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 148

Combination, in which R¹ is CN, R² is CF₂H, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 149

Combination, in which R¹ is CN, R² is CF₂H, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 150

Combination, in which R¹ is CN, R² is CF₃, R³ is H and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 151

Combination, in which R¹ is CN, R² is CF₃, R³ is CH₃ and the combinationof R⁴ and R⁵ corresponds in each case to one row of Table A

Table 152

Combination, in which R¹ is CN, R² is CF₃, R³ is C₃H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

Table 153

Combination, in which R¹ is CN, R² is CF₃, R³ is C₆H₅ and thecombination of R⁴ and R⁵ corresponds in each case to one row of Table A

TABLE A No. R⁴ R⁵ A-1 H H A-2 CH₃ H A-3 CH(CH₃)₂ H A-4 cC₃H₅ H A-5 C₆H₅H A-6 CH₂C₆H₅ H A-7 CHFCH₃ H A-8 1-C(O)NH₂—cC₃H₄ H A-9 1-CN—C₃H₄ H A-10CH₃ CH₃ A-11 CH(CH₃)₂ CH₃ A-12 cC₃H₅ CH₃ A-13 C₆H₅ CH₃ A-14 CH₂C₆H₅ CH₃A-15 CHFCH₃ CH₃ A-16 1-C(O)NH₂—cC₃H₄ CH₃ A-17 1-CN—C₃H₄ CH₃ A-18CH(CH₃)₂ CH(CH₃)₂ A-19 cC₃H₅ CH(CH₃)₂ A-20 C₆H₅ CH(CH₃)₂ A-21 CH₂C₆H₅CH(CH₃)₂ A-22 CHFCH₃ CH(CH₃)₂ A-23 1-C(O)NH₂—cC₃H₄ CH(CH₃)₂ A-241-CN—C₃H₄ CH(CH₃)₂ A-25 cC₃H₅ cC₃H₅ A-26 C₆H₅ cC₃H₅ A-27 CH₂C₆H₅ cC₃H₅A-28 CHFCH₃ cC₃H₅ A-29 1-C(O)NH₂—cC₃H₄ cC₃H₅ A-30 1-CN—C₃H₄ cC₃H₅ A-31C₆H₅ C₆H₅ A-32 CH₂C₆H₅ C₆H₅ A-33 CHFCH₃ C₆H₅ A-34 1-C(O)NH₂—cC₃H₄ C₆H₅A-35 1-CN—C₃H₄ C₆H₅ A-36 CH₂C₆H₅ CH₂C₆H₅ A-37 CHFCH₃ CH₂C₆H₅ A-381-C(O)NH₂—cC₃H₄ CH₂C₆H₅ A-39 1-CN—C₃H₄ CH₂C₆H₅ A-40 CHFCH₃ CHFCH₃ A-411-C(O)NH₂—cC₃H₄ CHFCH₃ A-42 1-CN—C₃H₄ CHFCH₃ A-43 1-C(O)NH₂—cC₃H₄1-C(O)NH₂—cC₃H₄ A-44 1-CN—C₃H₄ 1-C(O)NH₂—cC₃H₄ A-45 1-CN—C₃H₄ 1-CN—C₃H₄A-46 H CH₂OH A-47 CH₃ CH₂OH A-48 CH(CH₃)₂ CH₂OH A-49 cC₃H₅ CH₂OH A-50C₆H₅ CH₂OH A-51 CH₂C₆H₅ CH₂OH A-52 CHFCH₃ CH₂OH A-53 1-C(O)NH₂—cC₃H₄CH₂OH A-54 1-CN—C₃H₄ CH₂OH A-55 H CH(CH₃)OH A-56 CH₃ CH(CH₃)OH A-57CH(CH₃)₂ CH(CH₃)OH A-58 cC₃H₅ CH(CH₃)OH A-59 C₆H₅ CH(CH₃)OH A-60 CH₂C₆H₅CH(CH₃)OH A-61 CHFCH₃ CH(CH₃)OH A-62 1-C(O)NH₂—cC₃H₄ CH(CH₃)OH A-631-CN—C₃H₄ CH(CH₃)OH A-64 H C(CH₃)₂OH A-65 CH₃ C(CH₃)₂OH A-66 CH(CH₃)₂C(CH₃)₂OH A-67 cC₃H₅ C(CH₃)₂OH A-68 C₆H₅ C(CH₃)₂OH A-69 CH₂C₆H₅C(CH₃)₂OH A-70 CHFCH₃ C(CH₃)₂OH A-71 1-C(O)NH₂—cC₃H₄ C(CH₃)₂OH A-721-CN—C₃H₄ C(CH₃)₂OH A-73 H CH₂CH₂OH A-74 CH₃ CH₂CH₂OH A-75 CH(CH₃)₂CH₂CH₂OH A-76 cC₃H₅ CH₂CH₂OH A-77 C₆H₅ CH₂CH₂OH A-78 CH₂C₆H₅ CH₂CH₂OHA-79 CHFCH₃ CH₂CH₂OH A-80 1-C(O)NH₂—cC₃H₄ CH₂CH₂OH A-81 1-CN—C₃H₄CH₂CH₂OH A-82 H CH(CH₃)CH₂OH A-83 CH₃ CH(CH₃)CH₂OH A-84 CH(CH₃)₂CH(CH₃)CH₂OH A-85 cC₃H₅ CH(CH₃)CH₂OH A-86 C₆H₅ CH(CH₃)CH₂OH A-87 CH₂C₆H₅CH(CH₃)CH₂OH A-88 CHFCH₃ CH(CH₃)CH₂OH A-89 1-C(O)NH₂—cC₃H₄ CH(CH₃)CH₂OHA-90 1-CN—C₃H₄ CH(CH₃)CH₂OH A-91 H 2-furyl A-92 CH₃ 2-furyl A-93CH(CH₃)₂ 2-furyl A-94 cC₃H₅ 2-furyl A-95 C₆H₅ 2-furyl A-96 CH₂C₆H₅2-furyl A-97 CHFCH₃ 2-furyl A-98 1-C(O)NH₂—cC₃H₄ 2-furyl A-99 1-CN—C₃H₄2-furyl A-100 H 3-furyl A-101 CH₃ 3-furyl A-102 CH(CH₃)₂ 3-furyl A-103cC₃H₅ 3-furyl A-104 C₆H₅ 3-furyl A-105 CH₂C₆H₅ 3-furyl A-106 CHFCH₃3-furyl A-107 1-C(O)NH₂—cC₃H₄ 3-furyl A-108 1-CN—C₃H₄ 3-furyl A-109 HCH(OCH₃)₂ A-110 CH₃ CH(OCH₃)₂ A-111 CH(CH₃)₂ CH(OCH₃)₂ A-112 cC₃H₅CH(OCH₃)₂ A-113 C₆H₅ CH(OCH₃)₂ A-114 CH₂C₆H₅ CH(OCH₃)₂ A-115 CHFCH₃CH(OCH₃)₂ A-116 1-C(O)NH₂—cC₃H₄ CH(OCH₃)₂ A-117 1-CN—C₃H₄ CH(OCH₃)₂A-118 H CH₂ cC₆H₁₁ A-119 CH₃ CH₂ cC₆H₁₁ A-120 CH(CH₃)₂ CH₂ cC₆H₁₁ A-121cC₃H₅ CH₂ cC₆H₁₁ A-122 C₆H₅ CH₂ cC₆H₁₁ A-123 CH₂C₆H₅ CH₂ cC₆H₁₁ A-124CHFCH₃ CH₂ cC₆H₁₁ A-125 1-C(O)NH₂—cC₃H₄ CH₂ cC₆H₁₁ A-126 1-CN—C₃H₄ CH₂cC₆H₁₁ A-127 H CH₂C(CH₃)₃ A-128 CH₃ CH₂C(CH₃)₃ A-129 CH(CH₃)₂ CH₂C(CH₃)₃A-130 cC₃H₅ CH₂C(CH₃)₃ A-131 C₆H₅ CH₂C(CH₃)₃ A-132 CH₂C₆H₅ CH₂C(CH₃)₃A-133 CHFCH₃ CH₂C(CH₃)₃ A-134 1-C(O)NH₂—cC₃H₄ CH₂C(CH₃)₃ A-135 1-CN—C₃H₄CH₂C(CH₃)₃ A-136 H CH(CH₂CH₃)₂ A-137 CH₃ CH(CH₂CH₃)₂ A-138 CH(CH₃)₂CH(CH₂CH₃)₂ A-139 cC₃H₅ CH(CH₂CH₃)₂ A-140 C₆H₅ CH(CH₂CH₃)₂ A-141 CH₂C₆H₅CH(CH₂CH₃)₂ A-142 CHFCH₃ CH(CH₂CH₃)₂ A-143 1-C(O)NH₂—cC₃H₄ CH(CH₂CH₃)₂A-144 1-CN—C₃H₄ CH(CH₂CH₃)₂ A-145 H C(CH₃)₂SCH₃ A-146 CH₃ C(CH₃)₂SCH₃A-147 CH(CH₃)₂ C(CH₃)₂SCH₃ A-148 cC₃H₅ C(CH₃)₂SCH₃ A-149 C₆H₅C(CH₃)₂SCH₃ A-150 CH₂C₆H₅ C(CH₃)₂SCH₃ A-151 CHFCH₃ C(CH₃)₂SCH₃ A-1521-C(O)NH₂—cC₃H₄ C(CH₃)₂SCH₃ A-153 1-CN—C₃H₄ C(CH₃)₂SCH₃ A-154CH₂CH₂CF₂CH₂CH₂ A-155 CH₂CH₂CH₂ A-156 CH₂CH₂CH₂CH₂ A-157 CH₂CH₂CH₂CH₂CH₂A-158 CH₂OC(CH₃)₂OCH₂ A-159 CH₂OCH₂OCH₂

In a preferred embodiment of the invention, the compounds of formula Vare compounds, wherein R¹, R², R³, R⁴, and R⁵ are according to any oneof Tables 1 to 153 in combination with table A, entries A-1 to A-159,and wherein R⁶ is H.

In another preferred embodiment of the invention, the compounds offormula V are compounds, wherein R¹, R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is CN.

In yet another preferred embodiment of the invention, the compounds offormula V are compounds, wherein R¹, R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is CHF₂.

In yet another preferred embodiment of the invention, the compounds offormula V are compounds, wherein R¹, R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is CF₃.

Particularly preferred are compounds of formula V, wherein R¹, R², R³,R⁴, and R⁵ are according to any one of Tables 1 to 153 in combinationwith table A, entries A-1 to A-159, and wherein R⁶ is H.

If the meanings of R⁴ and R⁵ are different from each other and differentfrom R⁶, it is again noted that the compounds of formula V, for whichthe above combinations of substituents R¹, R², R³, R⁴ and R⁵ as well asR⁶ are preferred, may be present in the form of different stereoisomersbecause the —CR⁴R⁵R⁶ group is then chiral.

The same combinations of substituents R¹, R², R³, R⁴ and R⁵ as definedin the above tables 1 to 153 in combination with table A, entries A-1 toA-159, are also preferred for the compounds of formula IV.

Thus, in a preferred embodiment of the invention, the compounds offormula IV are compounds, wherein R¹, R², R³, R⁴, and R⁵ are accordingto any one of Tables 1 to 153 in combination with table A, entries A-1to A-159.

It is again noted that the wavy lines in generic formula IV indicatethat the substituents R⁴ and R⁵ as well as the substituents R³ and thehydrazone moiety may be present in both possible positions, so that allpossible E- and Z-isomers can be realized.

The same combinations of substituents R¹, R², R³, R⁴ and R⁵ as definedin the above tables 1 to 153 in combination with table A, entries A-1 toA-159, are also preferred for the precursors of the compounds of formulaIV, i.e. the compounds of formula I, II and III, provided that thesubstituents are present.

Thus, in one preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153.

Furthermore, in one preferred embodiment of the invention, the compoundsof formula II are compounds, wherein R⁴ and R⁵ are as defined in TablesA-1 to A-159.

Furthermore, in one preferred embodiment of the invention, the compoundsof formula I are compounds, wherein R⁴ and R⁵ are as defined in TablesA-1 to A-159.

As already indicated above, the compounds of formula IV are obtainablefrom the compounds of formula III by reacting them with compounds offormula II.

Apart from the substituents discussed above, the compounds of formulaIII further comprise a substituent X, which represents a leaving group.In principal, any leaving group, which is known in the art, e.g. in thecontext of nucleophilic substitution reactions, is suitable assubstituent X. In the process of preparing the compounds of formula IVas described herein, the substituent X of the compounds of formula IIIis is substituted by the amino group of hydrazine, so that thesubstituent is no longer contained in the compounds of formula IV.

In a preferred embodiment of the invention, in the compounds of formulaIII X is halogen, OH, C₁-C₁₀-alkoxy, C₃-C₁₀-cycloalkoxy,C₁-C₁₀-alkyl-C(O)O—, C₁-C₁₀-alkyl-S(O)₂O—, C₁-C₁₀-haloalkyl-S(O)₂O—,phenyl-S(O)₂O—, tolyl-S(O)₂O—, (C₁-C₁₀-alkyloxy)₂P(O)O—,C₁-C₁₀-alkylthio, C₃-C₁₀-cycloalkylthio, C₁-C₁₀-alkyl-C(O)S—, NH₂,C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, morpholino, N-methylpiperazinoor aza-C₃-C₁₀-cycloalkyl;

In a more preferred embodiment of the invention, in the compounds offormula III X is halogen, C₁-C₄-alkoxy, C₁-C₄-dialkylamino, morpholino,N-methylpiperazino or aza-C₅-C₆-cycloalkyl.

Preferably, X is halogen. As halogen, chlorine is particularlypreferred.

With regard to the C₁-C₄-dialkylamino groups, it is noted that the alkylchains may have identical or different chain lengths. Dimethylamino anddiethylamino groups are particularly preferred according to the presentinvention.

Furthermore, C₁-C₄-alkoxy groups, in particular C₁-C₂-alkoxy groups, areparticularly preferred according to the present invention.

The substituents R¹, R² and R³ of the compounds of formula III werealready discussed above.

Preferred compounds of formula III according to the present inventionare compounds, wherein R¹, R² and R³ are as defined above in any one oftables 1 to 153, and X is any one of Cl, OCH₃, OCH₂CH₃, N(CH₃)₂,N(CH₂CH₃)₂. It is to be understood that each combination between thesubstituents R¹, R² and R³ according to tables 1 to 153 and X being Cl,OCH₃, OCH₂CH₃, N(CH₃)₂, N(CH₂CH₃)₂ is suitable for the compounds offormula III according to the present invention.

Thus, in a preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153, and wherein X is Cl.

In another preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153, and wherein X is OCH₃.

In yet another preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153, and wherein X is OCH₂CH₃.

In yet another preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153, and wherein X is N(CH₃)₂.

In yet another preferred embodiment of the invention, the compounds offormula III are compounds, wherein R¹, R² and R³ are as defined inTables 1 to 153, and wherein X is N(CH₂CH₃)₂.

The compounds of formula II do not contain any further substituentsapart from the substituents R⁴ and R⁵, which were already discussedabove. It is again noted, however, that the substituents R⁴ and R⁵ maypreferably be selected in accordance with Table A above.

The compounds of formula II are obtainable from the compounds of formulaI by reacting them with hydrazine.

The compounds of formula I do not contain any further substituents apartfrom substituents R⁴ and R⁵, which were already discussed above, and mayparticularly preferably selected in accordance with Table A.

With regard to hydrazine as a reagent to be reacted with the compoundsof formula I in the process of the present invention, the following isnoted.

Hydrazine (also called diazane) is a compound with the formula H₂N—NH₂.Although hydrazine may principally be used in anhydrous form, it ispreferred that hydrazine is used in the form of an organic solution orthat hydrazine is used in the form of the monohydrate H₂N—NH₂×H₂O or inthe form of an aqueous solution of said monohydrate. It is particularlypreferred that hydrazine is used in the form of the monohydrateH₂N—NH₂×H₂O or in the form of an aqueous solution of said monohydrate.

If hydrazine is used in a solution in an organic solvent, the solvent ispreferably an alcohol, e.g. isopropanol, ethanol or methanol. Preferredconcentrations for alcoholic hydrazine solutions are in the range offrom 20% to 50% by weight, preferably 34% to 50% by weight of hydrazine,based on the total weight of the solution. It is particularly preferredthat hydrazine and the alcohol are present in a weight ratio of about1:1 in such alcoholic solutions.

If hydrazine is used in a solution in an aqueous solvent, the solvent ispreferably water, and the concentration typically refers to theconcentration of the monohydrate of hydrazine (H₂N—NH₂×H₂O). Preferredconcentrations for aqueous hydrazine monohydrate solutions are in therange of 45 to 100% by weight, preferably 60 to 100% by weight, e.g., 80to 100% or 70 to 90% by weight of hydrazine monohydrate based on thetotal weight of the solution. Preferably, hydrazine is used as 100%hydrazine monohydrate or as an aqueous solution of hydrazine monohydratewith a concentration of about 80 wt.-% of hydrazine monohydrate based onthe total weight of the solution.

Alternatively, hydrazine may be used in the form of a salt. Hydrazinecan easily be converted into salts by treatment with mineral or organicacids such as sulfuric acid, hydrochloric acid or acetic acid to give,e.g. salts of the formula [H₂N—NH₃]⁺HSO₄ ⁻, [H₂N—NH₃]⁺Cl⁻ or[H₂N—NH₃]⁺[O(C═O)CH₃]⁻, respectively. In certain preferred embodiments,hydrazine may be used in the form of an acetate or hydrochloride salt inthe process according to the present invention. The salt may be added tothe reaction mixture as a solid or in solution in an organic or aqueoussolvent, e.g. in methanol, ethanol, isopropanol or water.

As already indicated above, the compounds of formula V may be present ascompounds of formula Va, Vb or Vc.

In principal, the same combinations of substituents R¹, R², R³, R⁴ andR⁵ as defined in the above tables 1 to 153 in combination with table A,entries A-1 to A-159 are also preferred for the compounds of formulaeVa, Vb and Vc and the compounds, which are obtainable from the compoundsof formula Vc, namely the compounds of formulae VI and VIII. It isnoted, however, that these generic formulae are already pre-defined interms of the substituent R¹, so that only the specific combinations ofR², R³, R⁴ and R⁵ may be derived from the above tables.

The compounds of formula Va, Vb and Vc fall under the definition of thecompounds of formula V, if R¹ is selected as such that R¹ is CN(compound of formula Vb) or C(O)OR^(c) (compound of formula Va) orC(O)OH (compound of formula Vc). If R¹ in the compounds of formula V isC(O)OR^(c), it is further preferred that R^(c) is C₁-C₄-alkyl, e.g. CH₃,CH₂CH₃, C(CH₃)₃, or that R¹ is aryl-C₁-C₄-alkyl, e.g. CH₂C₆H₅.

For the remaining substituents, the same substituent definitions arepreferred as discussed above in tables 1 to 153 in combination withtable A. Furthermore, R⁶ is preferably H, CN, CHF₂, or CF₃.

Thus, in one preferred embodiment of the invention, the compounds offormula Vb are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H.

Furthermore, in one preferred embodiment of the invention, the compoundsof formula Va are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein R^(c) is CH₃.

In another preferred embodiment of the invention, the compounds offormula Va are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein R^(c) is CH₂CH₃.

In another preferred embodiment of the invention, the compounds offormula Va are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein R^(c) is C(CH₃)₃.

In another preferred embodiment of the invention, the compounds offormula Va are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein R^(c) is CH₂C₆H₅.

Moreover, in one preferred embodiment of the invention, the compounds offormula Vc are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H.

Further to the above discussed preferred substituent combinations, itcan be preferred for the compounds of formula Va, Vb and Vc that

R² is CH₃ or halomethyl,

R³ is H,

R⁴ is C₁-C₄-alkyl, C₁-C₂-haloalkyl, or C₃-cycloalkyl, wherein thecycloalkyl group is preferably substituted with one substituent selectedfrom CN and C(O)NH₂,

R⁵ is C₁-C₂-alkyl or C₃-C₄-cycloalkyl,

or R⁴ and R⁵ together with the carbon atom to which they are attachedform a 6-membered carbocycle, which is partially or fully halogenated,preferably fluorinated, and

R⁶ is H.

In view of the fact that the above compounds of formulae Va, Vb and Vcare versatile reaction tools for obtaining further pyrazole derivatives,the substituents of the compounds of formula V are particularlypreferably selected as such that R² is CH₃, R³ is H, R⁶ is H and theremaining substituent definitions are selected as indicated in one ofthe rows B-1 to B-30 of Table B.

TABLE B R¹ R⁴ R⁵ B-1 CN CH(CH₃)₂ CH₃ B-2 CN CHFCH₃ CH₃ B-3 CN 1-CN—cC₃H₄CH₃ B-4 CN 1-C(O)NH₂—cC₃H₄ CH₃ B-5 CN CH₂CH₂CF₂CH₂CH₂ B-6 C(O)OCH₃CH(CH₃)₂ CH₃ B-7 C(O)OCH₃ CHFCH₃ CH₃ B-8 C(O)OCH₃ 1-CN—cC₃H₄ CH₃ B-9C(O)OCH₃ 1-C(O)NH₂—cC₃H₄ CH₃ B-10 C(O)OCH₃ CH₂CH₂CF₂CH₂CH₂ B-11C(O)OCH₂CH₃ CH(CH₃)₂ CH₃ B-12 C(O)OCH₂CH₃ CHFCH₃ CH₃ B-13 C(O)OCH₂CH₃1-CN—cC₃H₄ CH₃ B-14 C(O)OCH₂CH₃ 1-C(O)NH₂—cC₃H₄ CH₃ B-15 C(O)OCH₂CH₃CH₂CH₂CF₂CH₂CH₂ B-16 C(O)OC(CH₃)₃ CH(CH₃)₂ CH₃ B-17 C(O)OC(CH₃)₃ CHFCH₃CH₃ B-18 C(O)OC(CH₃)₃ 1-CN—cC₃H₄ CH₃ B-19 C(O)OC(CH₃)₃ 1-C(O)NH₂—cC₃H₄CH₃ B-20 C(O)OC(CH₃)₃ CH₂CH₂CF₂CH₂CH₂ B-21 C(O)OCH₂C₆H₅ CH(CH₃)₂ CH₃B-22 C(O)OCH₂C₆H₅ CHFCH₃ CH₃ B-23 C(O)OCH₂C₆H₅ 1-CN—cC₃H₄ CH₃ B-24C(O)OCH₂C₆H₅ 1-C(O)NH₂—cC₃H₄ CH₃ B-25 C(O)OCH₂C₆H₅ CH₂CH₂CF₂CH₂CH₂ B-26C(O)OH CH(CH₃)₂ CH₃ B-27 C(O)OH CHFCH₃ CH₃ B-28 C(O)OH 1-CN—cC₃H₄ CH₃B-29 C(O)OH 1-C(O)NH₂—cC₃H₄ CH₃ B-30 C(O)OH CH₂CH₂CF₂CH₂CH₂

Rows B-1 to B-5 correspond to preferred compounds of formula Vb, rowsB-6 to B-25 correspond to preferred compounds of formula Va and rowsB-26 to B-30 correspond to preferred compounds of formula Vc, which maybe used in the process of the present invention.

As already indicated above, the compounds of formula Va and Vb can beobtained from the compounds of formula IV according the presentinvention. The compounds of formula Vc are obtainable from the compoundsof formula Va or Vb. Alternatively, the compounds of formula Vc maydirectly be obtained from the compounds of formula IV according thepresent invention.

The compounds of formula Vc may be further converted into compounds offormula VI according to the present invention.

Apart from the substituents discussed above, the compounds of formula VIfurther comprise a substituent X¹, which represents a leaving group. Inprincipal, any leaving group, which is known in the art, e.g. in thecontext of activated carboxylic acid derivatives, is suitable assubstituent X¹.

For example, X¹ may be a leaving group, which is based on a peptidecoupling reagent. Suitable peptide coupling reagents are described byHan et al. in Tetrahedron 60 (2004) 2447-2467.

In this regard, N,N′-bis(2-oxo-3-oxazolidinyl)-phosphinic chloride(BOP—Cl) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) are preferred according to the presentinvention.

Furthermore, X¹ may be a leaving group selected from active esters,azide and halogens.

In a preferred embodiment of the invention,

X¹ is halogen, N₃, p-nitrophenoxy, or pentafluorophenoxy.

Preferably, X¹ is halogen, in particular Cl.

Thus, in one preferred embodiment of the invention, the compounds offormula VI are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein X¹ is Cl.

In another preferred embodiment of the invention, the compounds offormula VI are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein X¹ is N₃.

In another preferred embodiment of the invention, the compounds offormula VI are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein X¹ is p-nitrophenoxy.

In another preferred embodiment of the invention, the compounds offormula VI are compounds, wherein R², R³, R⁴, and R⁵ are according toany one of Tables 1 to 153 in combination with table A, entries A-1 toA-159, and wherein R⁶ is H, and wherein X¹ is pentafluorophenoxy.

The compounds of formula VI may be further converted into compounds offormula VIII.

In the process of preparing the compounds of formula VIII as describedabove, the substituent X¹ of the compounds of formula VI is substitutedby the amine group of the N-(het)arylamine of formula VII, so that thesubstituent is no longer contained in the compounds of formula VIII.

However, apart from the remaining substituents discussed above, thecompounds of formula VIII further comprise the N-(het)arylamide group,wherein the amide nitrogen atom is substituted by R^(1N) and the(het)aryl group comprises a substituent U and substituents R^(P1),R^(P2) and R^(P3). The same substituents are also present in thecompounds of formula VII, with which the compounds of formula VI may bereacted to give the compounds of formula VIII.

In a preferred embodiment of the invention,

U is N or CH;

R^(P1), R^(P2), R^(P3) are H; and

R^(1N) is H, C₁-C₂-alkyl or C₁-C₂-alkoxy-C₁-C₂-alkyl.

In particular, the following combinations of substituents U, R^(P1),R^(P2), R^(P3) and R^(1N) according to Table C are preferred in thecompounds of formula VII and VIII.

TABLE C U R^(P1), R^(P2), R^(P3) R^(1N) C-1 N H H C-2 N H CH₃ C-3 N HCH₂CH₃ C-4 N H CH₂OCH₃ C-5 N H CH₂OCH₂CH₃ C-6 N H CH₂CH₂OCH₃ C-7 N HCH₂CH₂OCH₂CH₃ C-8 CH H H C-9 CH H CH₃ C-10 CH H CH₂CH₃ C-11 CH H CH₂OCH₃C-12 CH H CH₂OCH₂CH₃ C-13 CH H CH₂CH₂OCH₃ C-14 CH H CH₂CH₂OCH₂CH₃

Thus, in a preferred embodiment of the invention, the compounds offormula VII are compounds, wherein U, R^(P1), R^(P2), R^(P3), and R^(1N)are as defined in any one of rows C-1 to C-14 of table C.

Furthermore, in a preferred embodiment of the invention, the compoundsof formula VIII are compounds, wherein R², R³, R⁴, and R⁵ are accordingto any one of Tables 1 to 153 in combination with table A, entries A-1to A-159, and wherein R⁶ is H, and wherein U, R^(P1), R^(P2), R^(P3),and R^(1N) are as defined in any one of rows C-1 to C-14 of table C.

As already indicated above, the present invention is also directed tocompounds of formulae Va, Vb, Vc and VI.

In one embodiment, the present invention relates to a compound offormula Va or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H;

and wherein

R^(c) is C₁-C₄-alkyl or aryl-C₁-C₄-alkyl, or wherein R^(c) together withthe C(O)O group forms a salt [C(O)O]⁻NR₄ ⁺, [C(O)O]⁻M_(a) or[C(O)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali metal and M_(ea) is analkaline earth metal; and wherein the substituents R at the nitrogenatom are independently of each other selected from H, C₁-C₁₀-alkyl,phenyl and phenyl-C₁-C₄-alkyl.

If R^(c) together with the C(O)O group forms a salt, the salt ispreferably selected from [C(O)O]⁻NH₄ ⁺, [C(O)O]⁻Na⁺, [C(O)O]⁻K+,[C(O)O]⁻½Ca²⁺ and [C(O)O]⁻½Mg²⁺, and is particularly preferably[C(O)O]⁻Na⁺. If R^(c) together with the C(O)O group forms a salt, thisis to be understood as a carboxylate salt, wherein the negative chargeis delocalized in the carboxylate group [C(O)O]⁻.

If R^(c) is selected as such that the C(O)OR^(c) group is an estergroup, it is preferred that R^(c) is C₁-C₄-alkyl or benzyl, morepreferably, ethyl or tert-butyl.

It is particularly preferred according to the invention that R^(c) isselected as such that the C(O)OR^(c) group is an ester group. In thiscontext, C₁-C₄-alkyl or benzyl ester groups are particularly preferred.

In another embodiment, the present invention relates to a compound offormula Vb or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H.

In yet another embodiment, the present invention relates to a compoundof formula Vc or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H.

In yet another embodiment, the present invention relates to a compoundof formula VI or a salt, stereoisomer, tautomer or N-oxide thereof

wherein

R² is CH₃, R₃ is H, R⁴ is CH(CH₃)₂, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is CHFCH₃, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-CN-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ is 1-C(O)NH₂-cC₃H₄, R⁵ is CH₃ and R⁶ is H; or

R² is CH₃, R₃ is H, R⁴ and R⁵ together are CH₂CH₂CF₂CH₂CH₂, and R⁶ is H;

and wherein

X¹ is a leaving group.

Suitable leaving groups include leaving groups, which are known in theart in the context of activated carboxylic acid derivatives.

For example, X¹ may be a leaving group, which is based on a peptidecoupling reagent. Suitable peptide coupling reagents are described byHan et al. in Tetrahedron 60 (2004) 2447-2467. In this regard,N,N′-bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (BOP—Cl) andO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) are preferred according to the presentinvention.

Furthermore, X¹ may be a leaving group selected from active esters,azide and halogens.

Preferably, X¹ is selected from halogen, N₃, p-nitrophenoxy andpentafluorophenoxy, and more preferably, X¹ is halogen, and particularlypreferably X¹ is Cl.

As already indicated above, the process of the present invention coversthe preparation of a compound of formula V by cyclizing a compound offormula IV by reacting it with a reagent comprising a R⁶ group. Saidreaction step provides for the benefits of the present invention, namelythe versatile and convenient provision of compounds of formula V,thereby preferably ensuring regioselectivity. Preferably, the process ofthe present invention also includes the preparation of the compounds offormula IV, so that in particular a reaction sequence of the followingsteps (b) and (c) or the steps (a), (b) and (c) is covered by thepresent invention:

(a) I→II:

(b) II+III→IV:

(c) IV→V:

It is emphasized that the above reaction steps may not only be performedseparately, i.e. under isolation of the compounds of formulae II and IV,but that the reaction steps may also be performed in a one-pot reaction,i.e. without isolating the compounds of formulae II and/or IV. Oneoption is that steps (a), (b) and (c) are combined in a one-potreaction, e.g. by combining the compounds of formula I with hydrazine,so that first the compound of formula II is in situ formed, then addingthe compound of formula III to give the compound of formula IV in situ,and then adding the reagent comprising the R⁶ group to give a compoundof formula V. Another option is that steps (a) and (b) are performed ina one-pot reaction and the compound of formula IV is isolated, and thatthen step (c) is performed. And yet another option is that step (a) isperformed as a first step and the compound of formula II is isolated,and that then steps (b) and (c) are then performed in a one-potreaction.

Furthermore, it is emphasized that the reactions may be performed on atechnical scale. Preferably, the reactants are converted equally welland only minor deviations in terms of yield are observed.

As also already discussed above, the compounds of formula V areversatile reaction tools for the preparation of pesticidally activeagents. For example, if the compounds of formula V are compounds offormula Va or Vb, these compounds may be converted into compounds offormula Vc. The compounds of formula Vc, which can either be obtainedfrom the compounds of formula Va or Vb or as a reaction product of theabove reaction step (c), can then be further converted into compounds offormula VI. In a further reaction step, the compounds of formula VIIImay then be obtained. Thus, the following reaction sequence comprisingstep (d), preferably step (d) and step (e), and particularly preferablysteps (d), (e) and (f), may be performed subsequent to the abovereaction sequence according to the present invention.

(d) Va or Vb→Vc:

(e) Vc→VI:

(f) VI+VII→VIII:

It is noted that also steps (e) and (f) may be performed as a one-potreaction so that the activated compound VI does not have to be isolatedprior to the amidation reaction.

The above reaction steps of the process of the invention will bedescribed hereinafter, wherein it will be referred to the steps (a),(b), (c), (d), (e) and (f) as indicated above with step (c) being theessential step of the process of the present invention.

The reaction steps of the process of the invention as describedhereinafter are performed in reaction vessels customary for suchreactions, the reactions being carried out in a continuous,semi-continuous or batchwise manner.

In general, the particular reactions will be carried out underatmospheric pressure. The reactions may, however, also be carried outunder reduced pressure.

The temperatures and the duration times of the reactions may be variedin broad ranges, which the person skilled in the art knows fromanalogous reactions. The temperatures often depend on the refluxtemperature of the solvents. Other reactions are preferably performed atroom temperature, i.e. at about 25° C., or under ice cooling, i.e. atabout 0° C. The end of the reaction can be monitored by methods known toa person skilled in the art, e.g. thin layer chromatography or HPLC.

If not otherwise indicated, the molar ratios of the reactants, which areused in the reactions, are in the range of from 0.2:1 to 1:0.2,preferably from 0.5:1 to 1:0.5, more preferably from 0.8:1 to 1:0.8.Preferably, equimolar amounts are used.

If not otherwise indicated, the reactants can in principle be contactedwith one another in any desired sequence.

The person skilled in the art knows when the reactants or reagents aremoisture sensitive, so that the reaction should be carried out underprotective gases such as under a nitrogen atmosphere, and dried solventsshould be used.

The person skilled in the art also knows the best work-up of thereaction mixture after the end of the reaction.

In the following, the process of the invention is described in furtherdetail.

The reaction conditions for step (a) of the process are as follows.

In step (a) of the process of the invention, a compound of formula I isreacted with hydrazine to give a compound of formula II. Said reactionis a hydrazone formation, which can be performed under reactionconditions known in the art. In particular, the reaction can be carriedout by a process, wherein hydrazine monohydrate or a solution ofhydrazine, is reacted with a compound of formula I either in the absenceof a solvent or in an aqueous or organic solvent, wherein a basic or anacidic catalyst may optionally be present.

In a preferred embodiment the reaction is conducted in the absence of asolvent.

In a preferred embodiment the reaction is conducted in the absence of acatalyst.

Suitable reaction temperatures for the reaction are in the range of from0° C. to 80° C., preferably from 15° C. to 50° C., more preferably from20 to 25° C. In certain situations it can be preferred to start at alower temperature of from 20 to 25° C. for about 1 hour and then heatthe reaction mixture to a higher temperature of from 50 to 80° C. Inother situations, it can be preferred to start at a medium temperatureof from 30 to 50° C. for about 1 hour and then stir the reaction mixtureat a temperature of from 20 to 25° C.

The overall reaction times may vary in a broad range, e.g. from 1 hourto 3 days. It is therefore preferred that the reaction is monitored byanalytical methods and stopped after complete conversion of the compoundof formula I into formula II.

The compound of formula I is commercially available or can be preparedby methods known in the art.

As already indicated above, hydrazine is preferably provided in the formof the monohydrate or in the form of a solution of said monohydrate inwater. Preferred concentrations for aqueous hydrazine monohydratesolutions are in the range of 45 to 100% by weight, preferably 60 to100% by weight, e.g., 80 to 100% or 70 to 90% by weight of hydrazinemonohydrate based on the total weight of the solution. Preferably,hydrazine is used as 100% hydrazine monohydrate or as an aqueoussolution of hydrazine monohydrate with a concentration of about 80 wt.-%of hydrazine monohydrate based on the total weight of the solution.

Preferably, hydrazine is used at least in stochiometric amounts.Preferably, hydrazine is used in amounts in the range of from 1.0 to10.0 mol, preferably from 1.0 to 2.0 mol, more preferably from 1.0 to1.5 mol, per mol of the compound of formula I.

For practical reasons, it is preferred that the compound of formula I isadded to hydrazine monohydrate or a solution thereof and not vice versa,so that it is avoided that an excess of the compound of formula Icompared to hydrazine is present in the reaction mixture upon mixing thetwo components.

If a solvent is present, it is preferred that the solvent is an organicsolvent, either an aprotic or a protic solvent or a mixture thereof.Suitable aprotic solvents include aromatic solvents, ethers, or mixturesthereof. Preferred aromatic solvents are e.g. benzene, toluene, xylene(ortho-xylene, meta-xylene or para-xylene), mesitylene, chlorobenzene,1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, ormixtures thereof. Preferred ethers are open-chained and cyclic ethers,in particular diethyl ether, methyl-tert-butyl-ether (MTBE),2-methoxy-2-methylbutane, cyclopentylmethylether, 1,4-dioxane,tetrahydrofuran, 2-methyltetrahydrofuran, or mixtures thereof. Proticsolvents are typically preferred as solvents. Suitable protic solventsare C₁-C₄-alkanols such as methanol, ethanol, propanol and isopropanol,C₂-C₄-alkandiols, such as ethylene glycol or propylene glycol, and etheralkanols such as diethylene glycol, and mixtures thereof. Particularlypreferred are C₁-C₄-alkanols, e.g. methanol, ethanol, isopropanol,butanol, or mixtures thereof, in particular ethanol.

The reaction may also be performed in the presence of an acidic or basiccatalyst. Preferred acid catalysts include HCl in H₂O, HCl in MeOH, HClin dioxane; H₂SO₄, H₃PO₄ and salts of H₂SO₄ and H₃PO₄; aromatic sulfonicacids such as toluene sulfonic acid; alkylsulfonic acids, such as methylsulfonic acid; aromatic carboxylic acids such as benzoic acid;alkylcarboxylic acids such as acetic acid; salts of rare earth metals;and Lewis acids such as BF₃, BF₃×OEt₂, BF₃×SMe₂, TiCl₄, Ti(OiPr)₄. Apreferred acid catalyst is acetic acid. Preferred basic catalystsinclude BaO, CaO, MgCO₃, CaCO₃, Na₂CO₃, K₂CO₃ and NEt₃. A preferredbasic catalyst is BaO.

The acidic or basic catalyst is preferably used in amounts in the rangeof from 0.001 to 10 mol, preferably from 0.01 to 0.5 mol, morepreferably from 0.02 to 0.3 mol, per mol of the compound of formula I.For acidic catalysts, amounts in the range of from 0.05 to 0.2 mol permol of the compound of formula I can be preferred. For basic catalysts,amounts in the range of from 0.15 to 0.25 or from 0.2 to 0.3 mol per molof the compound of formula I can be preferred.

The reaction conditions for step (b) of the process of the invention areas follows.

In step (b), a compound of formula II is reacted with a compound offormula III to give a compound of formula IV. Said reaction correspondsto a substitution reaction at an α,β-unsaturated carbonyl compoundcomprising a leaving group in the β-position with a hydrazone acting asa nucleophile. The reaction can be performed under reaction conditionsknown in the art. In particular, the reaction can be carried out by aprocess, wherein the compound of formula II is reacted with a compoundof formula III either in the absence of a solvent or in an organicsolvent, wherein a basic catalyst may optionally be present.

Suitable reaction temperatures for the reaction are in the range of from−20° C. to 50° C., preferably from 15° C. to 40° C., more preferablyfrom 20 to 25° C. It is typically preferred that the compounds offormulae II and III are mixed with each other at temperatures below 0°C., preferably about −20° C., and that the mixture is then allowed towarm to a reaction temperature defined above.

The overall reaction times may vary in a broad range, e.g. from 1 hourto 1 day, preferably from 3 to 12 hours.

The compound of formula II may be provided as the crude product of step(a), i.e. without performing any purification steps prior to step (b),or as part of the reaction mixture obtained in step (a), to which thecompound of formula III may then be added.

The compound of formula III is commercially available or can be preparedby methods known in the art.

Preferably, the compound of formula III is used in amounts in the rangeof from 0.1 to 10.0 mol, preferably from 0.8 to 1.5 mol, more preferablyfrom 0.9 to 1.3 mol per mol of the compound of formula II.

If a solvent is present, it is preferred that the solvent is an organicsolvent, either an aprotic or a protic solvent or a mixture thereof.Suitable aprotic solvents include aromatic solvents, ethers, or mixturesthereof. Preferred aromatic solvents are e.g. benzene, toluene, xylene(orthoxylene, meta-xylene or para-xylene), mesitylene, chlorobenzene,1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, ormixtures thereof. Preferred ethers are open-chained and cyclic ethers,in particular diethyl ether, methyl-tert-butyl-ether (MTBE),2-methoxy-2-methylbutane, cyclopentylmethylether, 1,4-dioxane,tetrahydrofuran, 2-methyltetrahydrofuran, or mixtures thereof. Aparticularly suitable open-chained ether is e.g. MTBE. Protic solventsare typically preferred as solvents. Suitable protic solvents areC₁-C₄-alkanols such as methanol, ethanol, propanol and isopropanol,C₂-C₄-alkandiols, such as ethylene glycol or propylene glycol, and etheralkanols such as diethylene glycol, and mixtures thereof. Particularlypreferred are C₁-C₄-alkanols, e.g. methanol, ethanol, isopropanol,butanol, or mixtures thereof, in particular ethanol.

In principal, the reaction can easily be performed without having to usea catalyst. However, the reaction may also be performed in the presenceof a basic catalyst. Preferred basic catalysts include BaO, CaO, MgCO₃,CaCO₃, Na₂CO₃, K₂CO₃ and NEt₃.

If a basic catalyst is used, amounts in the range of from 0.01 to 2.0mol, preferably from 1.0 to 2.0 mol, per mol of the compound of formulaII are preferred.

The reaction conditions for step (c) of the process of the invention areas follows.

In step (c), a compound of formula IV is reacted with a reagentcomprising a R⁶ group to give a compound of formula V. The reactionconditions are described hereinafter. In particular, the reaction can becarried out by a process, wherein the compound of formula IV is reactedwith the reagent comprising the R⁶ group either in the presence of asolvent, wherein an acidic catalyst or a metal catalyst may optionallybe present.

The selection of the solvent depends on the type of the reagentcomprising the R⁶ group. In general organic solvents including aproticsolvents, such as aromatic solvents, ethers or mixtures thereof, andprotic solvents may be used. Preferred aromatic solvents are e.g.benzene, toluene, xylene (ortho-xylene, meta-xylene or para-xylene),mesitylene, chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene,1,4-dichlorobenzene, or mixtures thereof. Preferred ethers areopen-chained and cyclic ethers, in particular diethyl ether,methyl-tert-butyl-ether (MTBE), 2-methoxy-2-methylbutane,cyclopentylmethylether, 1,4-dioxane, tetrahydrofuran,2-methyltetrahydrofuran, or mixtures thereof. Preferred protic solventsare C₁-C₄-alkanols such as methanol, ethanol, propanol and isopropanol,C₂-C₄-alkandiols, such as ethylene glycol or propylene glycol, and etheralkanols such as diethylene glycol, and mixtures thereof. Particularlypreferred are C₁-C₄-alkanols, e.g. methanol, ethanol, isopropanol,butanol, or mixtures thereof.

If the reagent is reducing agent, preferably an ionic hydride donor,protic organic solvents can be preferred. Suitable protic solventsinclude C₁-C₄-alkanols such as methanol, ethanol, propanol andisopropanol, C₂-C₄-alkandiols, such as ethylene glycol or propyleneglycol, and ether alkanols such as diethylene glycol, and mixturesthereof. Particularly preferred are C₁-C₄-alkanols, e.g. methanol,ethanol, isopropanol, butanol, or mixtures thereof, in particularmethanol, ethanol and isopropanol. If the reducing agent is an ionichydride donor of higher reactivity, such as in case of Li⁺[AlH₄]⁻, itcan be preferred that the solvent is an aprotic organic solvent, e.g. anether solvent such as diethyl ether, methyl-tert-butyl ether (MTBE),2-methoxy-2-methylbutane, cyclopentylmethylether, 1,4-dioxane,tetrahydrofuran, 2-methyltetrahydrofuran, or mixtures thereof. Ethersolvents such as the ones listed above are also preferred, if thereagent is a non-ionic hydride donor.

On the other hand, protic solvents as mentioned above are againpreferred, if electron donors are used in combination with protons toact as a reducing agent because protons are required for the in situformation of hydrogen radicals.

If the reagent is an organometallic agent, aprotic organic solvents aretypically preferred. Suitable aprotic solvents include aliphatichydrocarbons, cycloaliphatic hydrocarbons, halogenated alkanes, aromatichydrocarbons, open-chained ethers, cyclic ethers, esters, aliphatic oralicyclic carbonates, in particular aromatic solvents and open-chainedand cyclic ethers. Preferred aprotic solvents are open-chained andcyclic ethers. Preferred open-chained ethers are diethyl ether,methy-tert-butyl ether (MTBE), 2-methoxy-2-methylbutane andcyclopentylmethylether.

Preferred cyclic ethers are tetrahydrofuran, 2-methyltetrahydrofuran and1,4-dioxane.

If the reagent is a nucleophilic reagent, both protic and aproticorganic solvents may be used. Protic solvents such as C₁-C₄-alkanols, inparticular methanol, ethanol and isopropanol, can again be preferred.

The reaction temperatures also depend on the type of the reagentcomprising the R⁶ group.

If the reagent is a reducing agent, the reaction temperatures may be inthe range of from −20° C. to 50° C., preferably from 10° C. to 30° C.,more preferably from 20° C. to 25° C. In certain situations, it can bepreferred to start the reaction at a higher temperature of from 30° C.to 50° C. and then continue the reaction at room temperature.

If the reagent is an organometallic reagent, lower reaction temperaturesof −78° C. to 0° C. may be suitable. Alternatively, the reactiontemperature may be in the range of from 0° C. to 50° C., preferably from10° C. to 30° C., more preferably from 20 to 25° C. In certainsituations it can be preferred to start at a lower temperature of about−78° C., −20° C. or 0° C. for about 1 hour and then allow the reactionmixture to warm to a temperature of from 0° C. to 25° C.

If the reagent is a nucleophilic reagent, the reaction temperatures maybe in the range of from 0° C. to 50° C., preferably from 10° C. to 30°C., more preferably from 20 to 25° C. Alternatively, it can be preferredthat the reaction mixture is heated, e.g. to a reaction temperature offrom 50° C. to 80° C.

The overall reaction times may vary in a broad range, preferably from 1hour to 4 days, e.g. from 4 hours to 8 hours, from 10 to 18 hours, from24 hours to 48 hours, or from 2 days to 4 days. It is thereforepreferred that the reaction is monitored by analytical methods andstopped after complete conversion of the compound of formula IV into thecompound of formula V.

The compound of formula IV can be provided as a crude product of step(b), i.e. without performing any purification steps prior to step (c),or as part of the reaction mixture obtained in step (b), to which thereagent comprising the R⁶ group may then be added.

The reagent comprising the R⁶ group is preferably used at least instoichiometric amounts, e.g. in amounts in the range of from 1.0 to 10.0mol, preferably from 1.0 to 2.0 mol per mol of the compound of formulaIV. If the reagent comprises more than one R⁶ groups, which may betransferred, it can also be sufficient to use sub-stoichiometricamounts, e.g. in the range of from 0.1 to less than 1.0 mol, preferably0.5 to less than 1.0 mol per mol of the compound of formula IV. Inprincipal, the reagent may therefore be used in amounts in the range offrom 0.1 to 10.0 mol per mol of the compound of formula IV. Preferably,the reagent is used in amounts of from 0.8 to 2.0 mol, more preferablyfrom 1.0 to 1.5 mol, per mol of the compound of formula IV.

If the reagent comprising the R⁶ group is in gaseous form, e.g. in caseof dihydrogen, the reagent is typically used in an excess by performingthe reaction in an atmosphere of the reagent comprising the R⁶ group. Acertain pressure may be applied, which preferably does not exceed 100bar for practical reasons.

The reagent comprising the R⁶ group may be added all at once or portionwise. In particular for the reagent being a reducing agent, e.g. anionic hydride donor such as Na⁺[B(CN)H₃]⁻, it is preferred that thereagent is provided in two or three portions.

If the amount of the reagent comprising the R⁶ group is used all atonce, it is preferred for practical reasons that the compound of formulaIV is added to the reagent comprising the R⁶ group.

Similarly, if the amount of the reagent comprising the R⁶ group is usedportion wise, it is preferred that the compound of formula IV is addedto the first portion of the reducing agent. Typically, about half of theamount of the reagent comprising the R⁶ group is used in this context.The mixture is then stirred for a certain reaction time of e.g. 10 to 18hours, and one or two further portions of the reagent are added lateron, so that the total amount of the reagent is finally added to thereaction mixture. The reaction mixture is then again stirred for acertain reaction time of, e.g., 10 to 18 hours, 12 to 24 hours, or 3 to4 days.

Preferred pH values for the reaction of the compounds of formula IV withthe reagent comprising the R⁶ group, e.g. an ionic hydride donor such asNa⁺[B(CN)H₃]⁻, are in the range of from 4 to 6.

In general, the reaction may be performed in the presence of an acidiccatalyst. This is particularly preferred, if the reagent comprising theR⁶ group is a reducing agent or a nucleophilic reagent. Preferred acidcatalysts include HCl in H₂O, HCl in MeOH, HCl in dioxane; H₂SO₄, H₃PO₄and salts of H₂SO₄ and H₃PO₄; aromatic sulfonic acids such as toluenesulfonic acid; alkylsulfonic acids, such as methyl sulfonic acid;aromatic carboxylic acids such as benzoic acid; alkylcarboxylic acidssuch as acetic acid; salts of rare earth metals; and Lewis acids such asBF₃, BF₃×OEt₂, BF₃×SMe₂, TiCl₄, Ti(OiPr)₄. Preferred acids catalystsfurther include aromatic sulfonic acids such as toluene sulfonic acid;alkylsulfonic acids, such as methyl sulfonic acid; aromatic carboxylicacids such as benzoic acid; alkylcarboxylic acids such as acetic acid;haloalkylcarboxylic acids such as trifluoroacetic acid, and mineralacids such as hydrogen chloride or sulfuric acid in methanol. Apreferred acid catalyst is acetic acid or HCl in MeOH. Acetic acid isparticularly preferred.

The acidic catalyst is preferably used in amounts in the range of from0.001 to 10 mol, preferably from 1.0 to 5.0 mol, e.g. 1.0 to 2.0 mol or2.0 to 4.0 mol, per mol of the compound of formula IV. For acetic acid,amounts of 1.0 to 3.0 mol per mol of the compound of formula IV arepreferred, and for HCl in MeOH, amounts of 1.0 to 5.0 mol per mol of thecompound of formula IV are preferred.

Alternatively or additionally, a metal catalyst may be present in thereaction mixture. Suitable metal catalysts include Cu, Pd, Pt, Ni, Fe,Rh, Ru either as the elements or in the form of a salt, and either pureor on an inert carrier. Suitable catalysts include Rayney-Nickel, Pd/C,Pt/C and the like. Preferred metal catalysts are selected from the groupconsisting of Rayney-Nickel, Pd/C, Pt/C, Ru/C, Rh/C, and PtO₂, inparticular from Rayney-Nickel, Pd/C, Pt/C, and PtO₂.

The resulting compounds of formula V, which can be obtained according tostep (c) of the process of the invention, can be purified by methodsknown in the art, e.g. by distillation, if esters of formula Va areprepared.

The reaction conditions for step (d) of the process of the invention areas follows.

In step (d), a compound of formula Va or Vb is converted into a compoundof formula Vc. Typically, said reaction may be understood as ahydrolysis reaction because an ester or a nitrile is hydrolyzed to givethe free acid. However, other conversion reactions of esters or nitrilesinto the free acids, such as the conversion of tert-butyl esters intothe free acids by the addition of trifluoroacetic acid, are also coveredby the invention.

If the reaction is a according to step (d) is a hydrolysis reaction, thereaction may be carried out by a process, wherein the compound offormula Va or Vb is reacted with water e.g. in the presence of a base orin the presence of an acid, or by a process, wherein the compound offormula Va or Vb is reacted with a water soluble base, preferably anoxo-base, in an aqueous solvent, or by a process, wherein the compoundof formula Va or Vb is reacted with a hydroxide in a protic aqueous ororganic solvent. Such hydrolysis reactions can be performed according toprocedures known in the art.

It is preferred according to the present invention that step (d) isperformed by dissolving a compound of formula Va in a protic solvent,either an aqueous solvent such as water or in a protic organic solvent,a such as a C₁-C₄-alkanol, e.g. methanol, ethanol or isopropanol, andadding a hydroxide.

Suitable hydroxides include alkali metal hydroxides such as lithium,sodium or potassium hydroxide, and mixtures thereof. Sodium hydroxide isparticularly preferred.

It is preferred that sodium hydroxide is used in amounts of from 1 to 10mol, preferably from 2.0 to 6.0 mol, e.g. 2.0 to 3.0 mol or 5.0 to 6.0mol, per mol of the compound of formula Va.

Suitable reaction temperatures may vary from 20 to 100° C., e.g. from 20to 25° C. or from 50 to 100° C.

The reaction times may vary from 1 hour to 2 days, e.g. from 1 to 3hours or from 12 hours to 24 hours or from 1 to 2 days.

The conversion of compounds of formula Va into compounds of formula Vccan be enhanced, and complete conversion can more easily be ensured, ifthe alcohol, which is formed upon hydrolysis of the compounds of formulaVa, is removed from the reaction mixture, e.g. by distillation.

The conversions of compounds of formula Vb into compounds of formula Vcis advantageously performed in an acidic medium, preferably in thepresence of H₂SO₄ or in the presence of HCl in MeOH. As intermediatecompounds, iminoester compounds are formed, which are then hydrolysed tothe desired acids of formula Vc.

The resulting compounds of formula Vc can be purified by methods knownin the art, e.g. by crystallization under suitable pH conditions.

The reaction conditions for steps (e) and (f) of the process are asfollows.

In step (e), the compound of formula Vc is activated by converting itinto the activated acid derivative of formula VI.

Suitable peptide coupling reagents, which may be used for introducingthe leaving group X¹ of the compounds of formula VI starting fromcompounds of formula V, are described by Han et al. in Tetrahedron 60(2004) 2447-2467. In this regard,N,N′-bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (BOP—Cl) andO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) are preferred according to the presentinvention.

In addition to the conversion of the compounds of formula Vc intoactivated acid derivatives of formula VI by means of these peptidecoupling reagents, it has also been described in the art how leavinggroups such as halogen, N₃, p-nitrophenoxy and pentafluorophenoxy can beintroduced into the compounds of formula Vc to give the correspondingcompounds of formula VI. In this regard, reference is made to WO2009/027393 and WO 2010/034737.

The compound of formula VI may either be directly converted into acompound of formula VIII or isolated. It is preferred, however, that thecompound of formula VI is directly converted into the compound offormula VIII.

The coversion of compounds of formula VI into compounds of formula VIIIIby reacting the compounds of formula VI with compounds of formula VIIIhas already been described in WO 2009/027393 and WO 2010/034737.

EXAMPLES I. Characterization

The characterization can be done by coupled High Performance LiquidChromatography/mass spectrometry (HPLC/MS), by NMR or by their meltingpoints.

HPLC/MS: the following methods A), B), C) and D) have been used, andwill be referred to further below.

-   A) Phenomenex Kinetex 1.7 μm XB-C18 100A; 50×2.1 mm; mobile phase:    A: water+0.1% trifluoroacetic acid (TFA); B: acetonitrile    (MeCN)+0.1% TFA; gradient: 5-100% B in 1.50 minutes; 100% B 0.20    min; flow: 0.8-1.0 mL/min in 1.50 minutes at 60° C. MS-method: ESI    positive.-   B) The gradient was 10-80% B in 1.15 min with a hold at 90% B for    0.4 min, 80-10% B in 0.01 min, and then hold at 10% B for 0.54 min    (1.0 mL/min flow rate). Mobile phase A was 0.0375% TFA in water,    mobile phase B was 0.018% TFA in MeCN. Column temperature was 40° C.    The column used for the chromatography was a 2.1×30 mm Halo C18    column (2.7 μm particles). MS-method: ESI positive.-   C) The gradient was 10-80% B in 1.15 min with a hold at 90% B for    0.4 min, 80-10% B in 0.01 min, and then hold at 10% B for 0.54 min    (1.0 mL/min flow rate). Mobile phase A was 0.0375% TFA in water,    mobile phase B was 0.018% TFA in MeCN. Column temperature was 40° C.    The column used for the chromatography was 2.0×30 mm phenomenex    Luna-C18 column (3 μm particles). MS-method: ESI positive.-   D) The gradient was 5-95% B in 0.7 min, 95-95% B in 0.45 min, 95-5%    B in 0.01 min, and then hold at 0% B for 0.44 min (1.5 mL/min flow    rate). Mobile phase A was 0.0375% TFA in water, mobile phase B was    0.018% TFA in MeCN. Column temperature was 40° C. The column used    for the chromatography was a Chromolith Flash RP-18e 25-2 mm column.    MS-method: ESI positive.

¹H-NMR: The signals are characterized by chemical shift (ppm) vs.tetramethylsilane, by their multiplicity and by their integral (relativenumber of hydrogen atoms given). The following abbreviations are used tocharacterize the multiplicity of the signals: m=multiplet, q=quartet,t=triplet, d=doublet and s=singlet.

Abbreviations used are: h for hour(s), min for minute(s) and roomtemperature for 20-25° C.

II. Preparation Examples Example 1 (Step (a)): 1-cyclohexylpropan-2-onehydrazone

A mixture of 1-cyclohexylpropan-2-one (10 g), hydrazine monohydrate (4.3g), barium oxide (2.8 g) and ethanol (100 ml) was refluxed for 14 h.After cooling to room temperature, diethyl ether (120 ml) was added. Themixture was filtered and the filtrate was evaporated to give the crudetitle compound (9.0 g, ca. 82% yield).

Example 2 (Step (b)): ethyl2-[[2-(2-cyclohexyl-1-methyl-ethylidene)hydrazino]methylene]-3-oxo-butanoate

Crude 1-cyclohexylpropan-2-one hydrazone (9.0 g) in ethanol (20 ml) wasadded to ethyl 2-(ethoxymethylene)-3-oxo-butanoate (11 g) in ethanol (80ml) at −20° C. within 40 min. After 30 min, the mixture was stirred atroom temperature over night and directly used in the next step.

Example 3 (step (c)): ethyl1-(2-cyclohexyl-1-methyl-ethyl)-5-methyl-pyrazole-4-carboxylate

Acetic acid (4.3 ml) was added to the reaction mixture from step 2.Sodium cyanoborohydride (2.4 g) was added portionwise within 30 min atroom temperature. After stirring over night, more acetic acid (2.5 ml)and more sodium cyanoborohydride (1.1 g) was added. After stirring overnight, again more acetic acid (3 ml) and more sodium cyanoborohydride(2.0 g) was added and the mixture was stirred at 50° C. for 3 h and thenconcentrated in vacuo. Water (80 ml) was added to the residue, and theaqueous phase was extracted three times with tert-butyl methyl ether.The combined organic extracts were washed with water, dried over sodiumsulfate and concentrated in vacuo to give the crude title compound (17g, ca. 80% purity, ca. 84% yield over 2 steps).

Example 4 (step (d)):1-(2-cyclohexyl-1-methyl-ethyl)-5-methyl-pyrazole-4-carboxylic acid

A mixture of crude ethyl1-(2-cyclohexyl-1-methyl-ethyl)-5-methyl-pyrazole-4-carboxylate (17 g,ca. 80% purity), aqueous sodium hydroxide solution (2 M, 56 ml) andethanol (150 ml) was stirred at room temperature for 2 d and thenconcentrated in vacuo. Water was added to the residue, and the aqueousphase was extracted three times with tert-butyl methyl ether.Concentrated hydrochloric acid was added under ice cooling to adjust thepH to ca. 4. The precipitate was filtered off, washed with water,triturated with tert-butyl methyl ether and dried in vacuo to give thetitle compound (5.3 g, ca. 43% yield, 30% yield over all 4 steps).¹H-NMR (d₆-DMSO): 7.76 (s, 1H), 4.46 (m, 1H), 2.49 (s, 3H), 1.84 (m,1H), 1.70 (d, 11.3 Hz, 1H), 1.66-1.43 (m, 5H), 1.31 (d, 6.6 Hz, 3H),1.09 (m, 3H), 0.89 (m, 3H).

In accordance with the above 4-step reaction procedure for preparingcompounds of formula V.c by performing

-   -   step (a) to provide compounds of formula II (Example 1),    -   step (b) to provide compounds of formula IV (Example 2),    -   step (c) to provide compounds of formula Va (Example 3), and    -   step (d) to provide compounds of formula Vc (Example 4),        a variety of compounds of formula V.a and V.c have been        prepared. The relevant substituents of the compounds of formula        V.c and its precursors are listed in the following table D.        Furthermore, the yields and analytical HPLC/MS data are        provided. The relevant reaction scheme is again depicted below.        Step (a):

Step (b):

Step (c):

Step (d):

TABLE D yield V.a V.a V.c V.c R^(c) X I → V.a RT m/z RT m/z # R⁵ R⁴ inV.a R² R³ in III.a [%] [min] Method [MH]⁺ [min] Method [MH]⁺  1 CH₃CH(CH₃)OH CH₂CH₃ CH₃ H OCH₂CH₃ 55 0.846 A 227.1 0.590 A 199.2  2 CH₃CH₂CH₂OH CH₂CH₃ CH₃ H OCH₂CH₃ 12 0.870 A 227.2 n/a n/a n/a  3 CH₃1-CN—cC₃H₄ CH₂CH₃ CH₃ H OCH₂CH₃ n/a 0.961 A 248.3 n/a n/a n/a  4 CH₃CH(CH₃)SCH₂CH(CH₃)₂ CH₂CH₃ CH₃ H OCH₂CH₃ 18 1.332 A 298.8 n/a n/a n/a  5CH₃ 2-furyl CH₂CH₃ CH₃ H OCH₂CH₃  5 1.064 A 249.5 n/a n/a n/a  6 CH₃2-furyl CH₂CH₃ CF₃ H OCH₂CH₃  3 1.091 A 302.8 n/a n/a n/a  7CH₂CH₂C(F₂)CH₂CH₂ CH₂CH₃ CH₃ H OCH₂CH₃ 85 1.116 A 273.5 0.837 A 245.1  8CH₂SCH₂CH₂CH(CN) CH₂CH₃ CH₃ H OCH₂CH₃ 35 0.894 A 280.0 n/a n/a n/a  9CH₃ CH(OCH₃)₂ CH₂CH₃ CH₃ H OCH₂CH₃ 85 1.002 A 257.5 0.709 A 228.8 10CH₂CH₂CH(OCH₂C₆H₅) CH₂CH₃ CH₃ H OCH₂CH₃ 16 1.189 A 314.8 n/a n/a n/a 1.225^(a) 11 CH₃ CH₂CH₂CHC(CH₃)₂ CH₂CH₃ CH₃ H OCH₂CH₃ 86 1.276 A 265.31.061 A 237.4 12 CH₃ 1-C(O)NH₂—cC₃H₄ CH₂CH₃ CH₃ H OCH₂CH₃ 24 0.841 A265.8 0.582 A 238.4 13 CH₃ CH₂cC₆H₁₁ CH₂CH₃ CH₃ H OCH₂CH₃ 69 1.381 A279.2 1.129 A 251.2 14 CH₃ CH₂C(CH₃)₃ CH₂CH₃ CH₃ H OCH₂CH₃ 96 1.310 A253.2 1.038 A 225.2 15 CH₃ CH(CH₂CH₃)₂ CH₂CH₃ CH₃ H OCH₂CH₃ n/a 1.315 A253.2 1.037 A 225.2 16 CH₂CH₂CH₂CH₂CH(CF₃) CH₂CH₃ CH₃ H OCH₂CH₃ 38 1.284A 305.1 1.040 A 277.1 17 CH₃ CH(CH₃)CH₂CH₂CH₃ CH₂CH₃ CH₃ H OCH₂CH₃ 771.310 A 253.2 1.046 A 225.2 18 CH₃ CH(CH₃)CH₂OH CH₂CH₃ CH₃ H OCH₂CH₃ 880.889 A 241.5 0.614 A 213.4 19 CH₃ CH(CH₃)₂ CH₂CH₃ CH₃ H OCH₂CH₃ 641.510 A 225.1 0.890 A 197.2 20 CH₃

CH₂CH3 CH₃ H OCH₂CH₃ 42 1.542  1.637^(a) C 349.2 n/a n/a n/a 21 CH₃

CH₂CH₃ CH₃ H N(CH₃)₂ 35 1.385  1.431^(a) C 293.2 1.111  1.150^(a) B265.2 22 CH₃

CH₂CH₃ CH₃ H N(CH₃)₂ 58 1.579 C 375.1 n/a n/a n/a 23 CH₃ C(CH₃)₂OHCH₂CH₃ CH₃ H N(CH₃)₂ 22 1.308 C 255.2 0.965 B 227.2 24 CH₃2-Br-2-CH₃—cC₃H₃ CH₂CH₃ CH₃ H OCH₂CH₃ 39 0.885  0.910^(a) D 315.1 n/an/a n/a 25 CH₂OC(CH₃)₂OCH₂ CH₂CH₃ CH₃ H N(CH₃)₂ 35 1.328 B 269.2 1.022 B241.1 26 CH₃ C(CH₃)₂SCH₃ CH₂CH₃ CH₃ H N(CH₃)₂ 33 1.328 C 271.2 1.253 B243.2 27 CH₃ 1-C(O)OC(CH₃)₃—cC₃H₄ CH₂CH₃ CH₃ H N(CH₃)₂ 39 0.934 D 323.2n/a n/a n/a 28 cC₃H₅ 1-CH₂OCH₂C₆H₅—cC₃H₄ CH₂CH₃ CH₃ H N(CH₃)₂ 44 0.947 D369.2 n/a n/a n/a 29 cC₃H₅ C(CH₃)₂CH₂OCH₂C₆H₅ CH₂CH₃ CH₃ H N(CH₃)₂ 660.990 D 371.2 n/a n/a n/a 30 CH₃

CH₂CH₃ CH₃ H N(CH₃)₂ 28 0.835 D 311.2 1.077 B 283.3 31 CH₃ CH₂OH C(CH₃)₃CH₃ H N(CH₃)₂ 41 0.697 D 241.1 n/a n/a n/a 32 CH₃ C(CH₃)(CO₂CH₂CH₃)C(CH₃)₃ CH₃ H N(CH₃)₂ 31 1.063 D 468.4 n/a n/a n/a (CH₂)₃NHCO₂C(CH₃)₃ 33CH₃ CH(CH₃)OH CH₂CH₃ CH₃ H N(CH₃)₂ 46 1.002 B 227.2 n/a n/a n/a 34 CH₃C(CH₃)₂OH C(CH₃)₃ CH₃ H N(CH₃)₂ 74 0.784 D 269.2 n/a n/a n/a 35 CH₃CH(CH₃)OH C(CH₃)₃ CH₃ H N(CH₃)₂ 69 0.757 D 255.2 n/a n/a n/a ^(a)mixtureof two diastereoisomers

The reaction procedure of Examples 1 to 4 refers compounds with asubstitution pattern according to entry 13 of table D.

The compounds according to the remaining entries were either preparedanalogously or according to the reaction conditions exemplified belowreferring to certain entries of the above table D. The reactionconditions exemplified below are not limited to the entries of table Dto which they refer, but were also suitable for the preparation of othercompounds disclosed in table D.

It is noted that steps (a) and (b), steps (b) and (c) were alsoperformed in a one-pot reaction in the preparation of certain compounds.

The following reaction conditions for steps (a), (b), (c) and (d) arerelevant for the preparation of the compounds listed above(abbreviations: rt=room temperature, i.e. 20 to 25° C., rfx=refluxtemperature, i.e. boiling point of the solvent; MeOH=methanol;EtOH=ethanol; AcOH=acetic acid; MTBE=methyltertbutyl ether;eq=equivalent).

Step (a):

corresponds to # entry x in table D conditions (a)-1 7 N₂H₄ × H₂O (1.2eq), BaO (0.02 eq), I (2 g/1 eq), MeOH (2 ml), rt, rfx overnight (a)-213 N₂H₄ × H₂O (1.2 eq), BaO (0.26 eq), EtOH (50 ml), I (10 g/1 eq), rt,rfx 14 h (a)-3 1 I (10 g/1 eq), BaO (0.26 eq), EtOH (80 ml), 10-20° C.,N₂H₄ × H₂O (1.2 eq), rt 1 h, 80° C. overnight (a)-4 12 N₂H₄ × H₂O (1eq), AcOH (0.17 eq), I (262 g/1 eq), EtOH (2200 ml), rt 3 days (a)-5 8N₂H₄ × H₂O (10 g/1.2 eq), EtOH (100 ml), I (262 g/1 eq), EtOH (100 ml),rt overnight (a)-6 10 I (3.6 g/1 eq), BaO (0.26 eq), EtOH (100 ml), rt,N₂H₄ × H₂O (1.2 eq), rt 3 days (a)-7 19 MeOH (3.25 eq), N₂H₄ × H₂O (1.28eq), BaO (0.02 eq), 33-47° C., I (2415 g/1 eq), 25° C. overnightSteps (a)+(b):

corresponds to entry x in # table D conditions (a) + (b)-1 3 N₂H₄ × H₂O(1 eq), AcOH (0.1 eq), I (1.376 g/1 eq), EtOH (15 ml), rt overnight;III.a (6.15 g/1.2 eq), rt overnight (a) + (b)-2 14 N₂H₄ × H₂O (1.2 eq),BaO (0.26 eq), EtOH (50 ml), rt, I (5 g/1 eq), rfx overnight; III.a (1eq), EtOH (50 ml), −20° C., II (5.5 g/1 eq), EtOH (20 ml), 30 min −20°C., rt overnightStep (b):

corresponds to # entry x in table D conditions (b)-1 9 III.a (1.1 eq),EtOH (60 ml), rt, II (12.5 g/ 1 eq), EtOH (40 ml), rt-37° C., rtovernight (b)-2 1 III.a (16.96 g/1 eq), EtOH (70 ml), 0-10° C., II (9.3g/1 eq), EtOH (30 ml), rt overnight (b)-3 12 III.a (450 g/1.51 eq), EtOH(3000 ml), AcOH (8.5 ml), II (221 g/1 eq), rt overnight (b)-4 19 III.a(609 g/1 eq), II (3818 g/1.09 eq) in MTBE (9.36% solution), 3 h rt-33°C. overnightStep (b)+(c):

corresponds to entry x in # table D conditions (b) + (c)-1 16 III.a(0.83 g/1 eq), EtOH (15 ml), −20° C., II (0.8 g/1 eq), EtOH (5 ml), −20°C. 30 min, rt over 3 days, AcOH (0.34 g/1.3 eq), 0-5° C. NaB(CN)H₃ (0.28g/1 eq), rt overnight, NaB(CN)H₃ (0.25 g), AcOH (0.4 ml), 6 h 40° C., rtovernight, 20 ml isopropanol, AcOH (1.3 eq), rt, NaB(CN)H₃ (1 eq), rtovernight, NaB(CN)H₃ (0.15 g), AcOH (0.2 ml), 6 h 40° C., rt overnight,NaB(CN)H₃ (0.1 g), 6 h 40° C., rt overnight (b) + (c)-2 17 III.a (7.12g/1 eq), EtOH (50 ml), rt, II (4.9 g/1 eq), EtOH (20 ml), rt overnight,AcOH (2.61 g/1.2 eq), rt, NaB(CN)H₃ (1.67 g/0.7 eq), rt over 3 days,isopropanol (100 ml), 10° C., AcOH (1.2 eq), 10° C., NaB(CN)H₃ (0.65eq), rt overnight, NaB(CN)H₃ (0.5 g), AcOH (0.5 ml), 6 h 40° C., rtovernight (b) + (c)-3 1 III.a (16.96 g/1 eq), EtOH (70 ml), 0-10° C., II(9.3 g/1 eq), EtOH (30 ml), rt overnight, EtOH (120 ml), AcOH (1.3 eq),10-17° C., NaB(CN)H₃ (1 eq), rt 3 days (b) + (c)-4 8 III.a (7.55 g/1eq), EtOH (50 ml), −20° C., II (5.2 g/1 eq), EtOH (20 ml), −20° C. 30min, rt over 3 days, MeOH (100 ml), AcOH (1.3 eq), 0-5° C., NaB(CN)H₃(2.51 g/1 eq), rt overnight, NaB(CN)H₃ (1.2 g), AcOH (1.5 ml), 6 h 40°C., rt overnight, NaB(CN)H₃ (1.5 g), AcOH (2 ml), 6 h 40° C., rtovernight, isopropanol (100 ml), NaB(CN)H₃ (1 eq), rt overnight (b) +(c)-5 15 III.a (10.86 g/1 eq), EtOH (80 ml), −20° C., II (9 g/1 eq),EtOH (20 ml), −20° C. 20 min, rt overnight, AcOH (4.53 g/1.3 eq),NaB(CN)H₃ (2.37 g/ 0.65 eq), rt overnight, 3 h 50° C., NaB(CN)H₃ (1.1g), AcOH (2.5 ml), rt overnight, NaB(CN)H₃ (2 g), AcOH (3 ml), 3 h 50°C. (b) + (c)-6 13 III.a (10.86 g/1 eq), EtOH (80 ml), −20° C., II (1eq), EtOH (20 ml), −20° C. 30 min, rt overnight, AcOH (4.53 g/1.3 eq),rt, NaB(CN)H₃ (2.37 g/ 0.65 eq), rt overnight, 3 h 50° C., NaB(CN)H₃(1.1 g), AcOH (2.5 ml), 3 h 50° C., rt overnight, NaB(CN)H₃ (2 g), AcOH(3 ml), 3 h 50° C. (b) + (c)-7 11 III.a (13.01 g/1 eq), EtOH (60 ml),rt, II (1 eq), EtOH (20 ml), rt overnight, AcOH (5.45 g/3.64 eq), 0-5°C., NaB(CN)H₃ (1.02 g/0.65 eq), rt 3 daysStep (c):

corresponds to # entry x in table D conditions (c)-1 9 IV.a (27.9 g/1eq), isopropanol (100 ml), rt, NaB(CN)H₃ (0.6 eq), AcOH (1.2 eq), rtovernight, NaB(CN)H₃ (0.6 eq), rt overnight (c)-2 10 IV.a (1 g/1 eq),EtOH (20 ml), rt, AcOH (2.4 eq), NaB(CN)H₃ (1.2 eq), rt over 3 days(c)-3 17 IV.a (9.5 g/1 eq), isopropanol (100 ml), 10° C., NaB(CN)H₃(0.65 eq), AcOH (1.2 eq) rt overnight, NaB(CN)H₃ (0.5 g), AcOH (0.5 ml),6 h 40° C., rt overnight (c)-4 18 IV.a (18 g/1 eq), MeOH (120 ml), AcOH(1.2 eq), rt, NaB(CN)H₃ (1 eq), rt overnight (c)-5 18 IV.a (15.7 g/1eq), isopropanol (100 ml), AcOH (1.25 eq), rt, NaB(CN)H₃ (1 eq), rt over3 days, AcOH (2.5 ml), NaB(CN)H₃ (1 g), 4 h 40° C., rt overnight (c)-6 7IV.a (1.9 g/1 eq), 0-5° C., NaB(CN)H₃ (0.65 eq), AcOH (1.3 eq), rtovernight, NaB(CN)H₃ (0.3 eq), rt over 3 days (c)-7 12 IV.a (100 g/1eq), MeOH (1400 ml), rt, NaB(CN)H₃ (2.19 eq), HCl (1N in MeOH, 1000 ml),40° C., rt overnight (c)-8 19 IV.a (889 g/1 eq), MeOH (3000 ml), AcOH(400 g), rt-30° C., NaB(CN)H₃ (1.09 eq), rt overnightStep (d):

corresponds to # entry x in table D conditions (d)-1 13 V.a (17 g/1 eq),EtOH (150 ml), NaOH (2M in H₂O, 4.49 g/2.3 eq), rt overnight, NaOH (2Min H₂O, 25 ml), rt 24 h (d)-2 1 V.a (15.3 g/1 eq), EtOH (80 ml), NaOH(2.5 eq), H₂O (40 ml), rt over-night (d)-3 12 V.a (120 g/1 eq), MeOH(1400 ml), NaOH (5.96 eq), H₂O (58.54 eq), rtovernight (d)-4 7 V.a (2.15g/1 eq), EtOH 30 ml), NaOH(2M in H₂O, 2.5 eq), 45° C. 2.5 h (d)-5 19NaOH (10% in H₂O, 3 eq), rt, V.a (724 g/1 eq), 1 h 95° C.

The invention claimed is:
 1. A process for preparing a pyrazole compound of formula V, or a salt, stereoisomer, tautomer or N-oxide thereof

comprising the step of cyclizing a hydrazone substituted α,β-unsaturated carbonyl compound of formula IV

by reacting it with a reagent comprising a R⁶ group, wherein R¹ is selected from H, halogen, CN, NO₂, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms be unsubstituted, may be partially or fully halogenated or may be substituted by 1, 2 or 3 identical or different substituents R^(x); OR^(a), SR^(a), C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y¹R^(d), NR^(e)R^(f), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl and aryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x); R² is selected from H, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms may be unsubstituted, may be partially or fully halogenated or may be substituted by 1, 2 or 3 identical or different substituents R^(x); C(Y)OR^(c), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl and aryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x); and R³ is selected from H, halogen, CN, NO₂, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms may be unsubstituted, may be partially or fully halogenated or may be substituted by 1, 2 or 3 identical or different substituents R^(x); OR^(a), SR^(a), C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y¹R^(d), NR^(e)R^(f), C(Y)NR^(g)R^(h), heterocyclyl, hetaryl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl, and aryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x); and wherein R⁴ and R⁵ are independently of each other selected from H, NO₂, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, wherein the C-atoms may be unsubstituted, may be partially or fully halogenated or may be substituted by 1, 2 or 3 identical or different substituents R^(x); C₁-C₁₀-haloalkyl, C₁-C₄-alkoxy-C₁-C₁₀-alkyl, wherein the C-atoms may be unsubstituted, or partially or fully substituted by identical or different substituents R^(y); C(Y)OR^(c), C(Y)NR^(g)R^(h), C(Y)NR^(i)NR^(e)R^(f), C₁-C₅-alkylen-OR^(a), C₁-C₅-alkylen-CN, C₁-C₅-alkylen-C(Y)OR^(c), C₁-C₅-alkylen-NR^(e)R^(f), C₁-C₅-alkylen-C(Y)NR^(g)R^(h), C₁-C₅-alkylen-S(O)_(m)R^(d), C₁-C₅-alkylen-S(O)_(m)NR^(e)R^(f), C₁-C₅-alkylen-NR^(i)NR^(e)R^(f), heterocyclyl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkenyl, hetaryl, aryl, heterocyclyl-C₁-C₅-alkyl, C₃-C₁₀-cycloalkyl-C₁-C₅-alkyl, C₃-C₁₀-cycloalkenyl-C₁-C₅-alkyl, hetaryl-C₁-C₅-alkyl, aryl-C₁-C₅-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents R^(y); groups -D-E, wherein D is a direct bond, C₁-C₆-alkylene, C₂-C₆-alkenylene, or C₂-C₆-alkynylene, which carbon chains can be partially or fully substituted by R^(n), and E is a non-aromatic 3- to 12-membered carbo- or heterocycle, which may contain 1, 2, 3, or 4 heteroatoms selected from N—R¹, O, and S, wherein S may be oxidized, which carbo- or heterocycle may be partially or fully substituted by R^(n); and groups -A-SO_(m)-G, wherein A is C₁-C₆-alkylene, C₂-C₆-alkenylene and C₂-C₆-alkynylene, wherein the C-atoms may be unsubstituted, or partially or fully substituted by R^(p), and G is C₁-C₄-haloalkyl or C₃-C₆-cycloalkyl which may be halogenated; or R⁴ and R⁵ together with the carbon atom to which they are attached form a 3- to 12-membered non-aromatic carbo- or heterocycle, which heterocycle may contain 1, 2, 3, 4, or 5 heteroatoms selected from N—R¹, O, and S, wherein S may be oxidized, and which carbo- or heterocycle may be partially or fully substituted by RR; and wherein the reagent comprising the R⁶ group is selected from the groups consisting of: (i) a reducing agent, wherein R⁶ is H, (ii) an organometallic reagent, wherein R⁶ is selected from C₁-C₆-fluoroalkyl, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₂-alkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenyl-C₁-C₂-alkyl, heterocyclyl, heterocyclyl-C₁-C₂-alkyl, aryl, aryl-C₁-C₂-alkyl, hetaryl, hetaryl-C₁-C₂-alkyl, wherein the carbon chains or cyclic moieties may be unsubstituted, partially or fully substituted by identical or different substituents R^(x), and (iii) a nucleophilic reagent of formula H—R⁶, M_(a) ⁺R⁶⁻ or ½M_(ea) ²⁺R⁶⁻, wherein M_(a) is an alkaline metal and M_(ae) is an alkaline earth metal, and wherein R⁶ is selected from the groups consisting of CN, OR^(a), SR^(a), NR^(e)R^(f), and groups of the general formula (i)

and wherein R^(a), R^(b) are independently of each other selected from H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4 or 5 substituents which, independently of each other, are selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; R^(c) is selected from H, C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cyclo-alkylmethyl, C₃-C₁₀-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₁₀-alkenyl, C₂-C₁₀-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may be substituted by 1, 2, 3, 4 or 5 substituents which, independently of each other, are selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; or R^(c) together with the C(Y)O group forms a salt [C(Y)O]⁻NR₄ ⁺, [C(Y)O]⁻M_(a) ⁺ or [C(Y)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali metal and M_(ea) is an alkaline earth metal, and wherein the substituents R at the nitrogen atom are independently of each other selected from H, C₁-C₁₀-alkyl, phenyl and phenyl-C₁-C₄-alkyl; R^(d) is selected from C₁-C₄-alkoxy, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; R^(e), R^(f) are independently of each other selected from H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkylmethyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkylsulfonyl, C₁-C₄-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, heterocyclylcarbonyl, heterocyclyl-C₁-C₄-sulfonyl, aryl, arylcarbonyl, arylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents which, independently of each other, are selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; or R^(e) and R^(f) together with the N atom to which they are bonded form a 5- or 6-membered, saturated or unsaturated heterocycle, which may be substituted by a further heteroatom being selected from O, S and N as a ring member atom and wherein the heterocycle may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; R^(g), R^(h) are independently of each other selected from H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl and hetaryl-C₁-C₄-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; R^(i) is selected from H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-methyl, C₃-C₆-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, aryl, and aryl-C₁-C₄-alkyl, wherein the aryl ring may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 substituents which are independently of each other selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy and C₁-C₄-haloalkoxy; R^(j) is halogen, OH, CN, C(O)NH₂, NO₂, C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-haloalkoxy, benzyloxy, S(O)_(m)R^(k), C₃-C₆-cycloalkyl, or a 3- to 6-membered heterocycle, which may contain 1 or 2 heteroatoms selected from N-R, O, and S, wherein S may be oxidized, which R^(j) groups are unsubstituted or partially or fully substituted by R^(m), and wherein two groups R^(j) connected to the same or adjacent ring atoms may together form a 3- to 6-membered carbo- or heterocycle which heterocycle may contain 1 or 2 heteroatoms selected from N-R, O, and S, wherein S may be oxidized, which cycles may be partially or fully substituted by R^(m) radicals; R^(k) is H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, or C₃-C₆-cycloalkyl, which cycle may be partially or fully substituted by R¹; R^(l) is H, halogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkylcarbonyl, or C₁-C₄-alkoxy-carbonyl; R^(m) is halogen, OH, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, or S(O)_(m)R^(k); R^(n) is halogen, CN, C(Y)OR^(c), C(O)NH₂, NO₂, C₁-C₂-alkyl, C₁-C₄-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkyliden, or S(O)_(m)R^(o), two adjacent groups R^(n) may form together with the atoms to which they are bonded a 3- to 8-membered carbo- or heterocycle, which may contain 1, 2, 3, or 4 heteroatoms selected from N—R^(l), O, and S, wherein S may be oxidized, which cyclic R^(n) moieties may be substituted by halogen, R^(o), or R^(l); R^(o) is H, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, or C₁-C₄-alkoxy; R^(p) is halogen, CN, C(O)NH₂, NO₂, C₁-C₂-alkyl, C₁-C₂-haloalkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, or C₁-C₂-haloalkoxy, or two groups R^(p) can together form a 3- to 6-membered carbo- or heterocyclic ring, which heterocycle contains 1 or 2 heteroatoms selected from N—R^(l), O, and S, wherein S may be oxidized, which carbo- or heterocyclic ring is unsubstituted or partly or fully substituted by groups R^(q); R^(q) is halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, or C₁-C₄-haloalkoxy; R^(r) and R^(s) are independently of each other selected from R^(b), OR^(c1), and NR^(g)R^(h); R^(c1) is C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-cycloalkylmethyl, C₃-C₁₀-halocycloalkyl, C₃-C₆-cycloalkenyl, C₃-C₆-cycloalkenylmethyl, C₃-C₆-halocycloalkenyl, C₂-C₁₀-alkenyl, C₂-C₁₀-haloalkenyl, C₂-C₄-alkynyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, heterocyclyl, heterocyclyl-C₁-C₄-alkyl, aryl, hetaryl, aryl-C₁-C₄-alkyl or hetaryl-C₁-C₄-alkyl, wherein the ring in the six last mentioned radicals may be unsubstituted or may be substituted by 1, 2, 3, 4 or substituents which, independently of each other, are selected from halogen, CN, C(O)NH₂, NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy or C₁-C₄-haloalkoxy; R^(t) is H or R^(a); R^(x) is halogen, CN, C(Y)OR^(c), C(Y)NR^(g)R^(h), NO₂, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, S(O)_(m)R^(d), S(O)_(m)NR^(e)R^(f), C₁-C₅-alkylen-NHC(O)OR^(c), C₁-C₁₀-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl, C₁-C₄-haloalkoxycarbonyl, C₃-C₆-cycloalkyl, 5- to 7-membered heterocyclyl, 5- or 6-membered hetaryl, aryl, C₃-C₆-cycloalkoxy, 3- to 6-membered heterocyclyloxy, or aryloxy, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 radicals R^(y); and R^(y) is selected from halogen, CN, C(Y)OR^(c), C(Y)NR^(g)R^(h), NO₂, C₁-C₄-alkyl, C₁-C₄-halo-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, benzyloxymethyl, S(O)_(m)R^(d), S(O)_(m)NR^(e)R^(f), C₁-C₄-alkylcarbonyl, C₁-C₄-haloalkylcarbonyl, C₁-C₄-alkoxycarbonyl, C₁-C₄-haloalkoxycarbonyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl and C₁-C₄-alkoxy-C₁-C₄-alkyl; and wherein Y is O or S; Y¹ is O, S, or N-R^(1a); R^(1a) is H, C₁-C₁₀-alkyl, C₃-C₁₂-cycloalkyl, aryl, or hetaryl; and m is 0, 1 or
 2. 2. The process according to claim 1, wherein R¹ is H, halogen, CN, NO₂, C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1, 2, or 3 identical or different substituents R^(x), C(Y)OR^(c), S(O)_(m)R^(d), S(O)_(m)Y^(I)R^(d), C₃-C₁₂-cycloalkyl, aryl, or hetaryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x); wherein R^(c) is H, C₁-C₄-alkyl or aryl-C₁-C₄-alkyl, or wherein R^(c) together with the C(Y)O group forms a salt [C(Y)O]⁻NH₄ ⁺, [C(Y)O]⁻M_(a) ⁺or [C(Y)O]⁻½M_(ea) ²⁺, wherein M_(a) is an alkali metal and M_(ea) is an alkaline earth metal; wherein R^(d) is C₁-C₄-alkyl, C₃-C₆-cycloalkyl, aryl, or hetaryl; wherein Y is O; and wherein Y¹ is O or NR^(1a), wherein R^(1a) is C₁-C₄-alkyl, C₃-C₆-cycloalkyl, aryl, or hetaryl; and wherein preferably R¹ is CN, C(Y)OR^(c), wherein Y is O, and R^(c) is C₁-C₄-alkyl or benzyl.
 3. The process according to claim 1, wherein R² is C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1, 2 or 3 identical or different substituents R^(x), C₃-C₁₂-cycloalkyl, aryl, or hetaryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x).
 4. The process according to claim 1, wherein R³ is H, C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1, 2 or 3 identical or different substituents R^(x), C₃-C₁₂-cycloalkyl, aryl, or hetaryl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x).
 5. The process according to claim 1, wherein R² and R³ are different from each other.
 6. The process according to claim 1, wherein R⁴ is selected from C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1, 2 or 3 identical or different substituents R^(x), and C₃-C₁₀-cycloalkyl, which may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents R^(y); and R⁵ is selected from C₁-C₁₀-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1, 2 or 3 identical or different substituents R^(x), and C₃-C₁₀-cycloalkyl, which may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents R^(y).
 7. The process according to claim 1, wherein the reagent comprising the R⁶ group is (i) a reducing agent selected from the group consisting of: (ia) an ionic hydride donor selected from the group consisting of complex hydrides of boron and aluminum, (ib) a non-ionic hydride donor selected from the group consisting of dihydrogen in combination with a metal catalyst, Hantzsch ester, 1,4-dihydrobenzol, isopropanol, formic acid, or ammonium formate, and (ic) an electron donor in combination with a proton, wherein an electrons is donated by a cathode or a metal selected from the group consisting of Li, Na, K, Mg, Zn, Fe and Al.
 8. The process according to claim 1, wherein R⁶ is selected from H, CN, and C₁-C₂-fluoroalkyl.
 9. The process according to claim 1, further comprising the step of preparing the hydrazone substituted α,β-unsaturated carbonyl compound of formula IV

by reacting an α,β-unsaturated carbonyl compound of formula III

with a hydrazone compound of formula II

wherein X is a leaving group.
 10. The process according to claim 9, wherein X is halogen, OH, C₁-C₁₀-alkoxy, C₃-C₁₀-cycloalkoxy, C₁-C₁₀-alkyl-C(O)O—, C₁-C₁₀-alkyl-S(O)₂O—, C₁-C₁₀-haloalkyl-S(O)₂O—, phenyl-S(O)₂O—, tolyl-S(O)₂O—, (C₁-C₁₀-alkyloxy)₂P(O)O—, C₁-C₁₀-alkylthio, C₃-C₁₀-cycloalkylthio, C₁-C₁₀-alkyl-C(O)S—, NH₂, C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, morpholino, N-methylpiperazino or aza-C₃-C₁₀-cycloalkyl.
 11. The process according to claim 9, further comprising the step of preparing the hydrazone compound of formula II

by reacting a carbonyl compound of formula I

with hydrazine or a salt thereof.
 12. The process according to claim 1, wherein the compound of formula V is a compound of formula Va or Vb

and wherein the process further comprises the step of converting the compound of formula Va or Vb into a compound of formula Vc

wherein R^(c) in formula Va is C₁-C₄-alkyl or aryl-C₁-C₄-alkyl.
 13. A process according to claim 1, wherein the process further comprises the step of converting a compound of formula Vc into a compound of formula VI

wherein X¹ is a leaving group selected from halogen, N₃, p-nitrophenoxy, and pentafluorophenoxy.
 14. The process according to claim 13, wherein the process further comprises the step of converting the compound of formula VI into a compound of formula VIII

by reacting the compound of formula VI with a compound of formula VII

wherein U is N or CR^(U); R^(P1), R^(P2), R^(P3), and R^(U) are independently of each other selected from H, halogen, C₁-C₄-alkyl, C₁-C₃-haloalkyl, C₁-C₄-alkoxy, C₁-C₃-haloalkoxy, C₁-C₄-alkylthio, C₁-C₃-halo-alkylthio, C₁-C₄-alkylsulfinyl, C₁-C₃-haloalkylsulfinyl, C₁-C₄-alkylsulfonyl, C₁-C₃-haloalkylsulfonyl, C₃-C₆-cycloalkyl, C₃-C₆-halocycloalkyl, C₂-C₄-alkenyl, C₂-C₄-haloalkenyl, C₂-C₄-alkynyl and C₁-C₄-alkoxy-C₁-C₄-alkyl; and R^(1N) is H, CN, C₁-C₁₀-alkyl, C₁-C₁₀-haloalkyl, C₃-C₁₀-cycloalkyl, C₃-C₁₀-halocycloalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-haloalkenyl, C₂-C₁₀-alkynyl, C₃-C₁₀-haloalkynyl, C₁-C₅-alkylen-CN, OR^(a), C₁-C₅-alkylen-OR^(a), C(Y)R^(b), C₁-C₅-alkylen-C(Y)R^(b), C(Y)OR^(c), C₁-C₅-alkylen-C(Y)OR^(c), S(O)₂R^(d), NR^(e)R^(f), C₁-C₅-alkylen-NR^(e)R^(f), C(Y)NR^(g)R^(h), C₁-C₅-alkylen-C(Y)NR^(g)R^(h), S(O)_(m)NR^(e)R^(f), C(Y)NR^(i)NR^(e)R^(f), C₁-C₅-alkylen-S(O)₂R^(d), C₁-C₅-alkylen-S(O)_(m)NR^(e)R^(f), C₁-C₅-alkylen-C(Y)NR^(i)NR^(e)R^(f), aryl, heterocyclyl, hetaryl, aryl-C₁-C₅-alkyl, C₃-C₁₀-cycloalkyl-C₁-C₅-alkyl, heterocyclyl-C₁-C₅-alkyl or hetaryl-C₁-C₅-alkyl, wherein the cyclic moieties may be unsubstituted or may be substituted by 1, 2, 3, 4, or 5 identical or different substituents selected from the radicals R^(y) and R^(x).
 15. The process according to claim 14, wherein U is N or CH; R^(P1), R^(P2), R^(P3) are H; and R^(1N) is H, C₁-C₂-alkyl or C₁-C₂-alkoxy-C₁-C₂-alkyl.
 16. The process according to claim 6, wherein R⁴ is selected from C₁-C₄-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1 or 2 identical or different substituents R^(x), wherein R^(x) is selected from CN and C(O)NH₂, and C₃-C₆-cycloalkyl, which may be unsubstituted or may be substituted by 1, 2, or 3 identical or different substituents R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂; and R⁵ is selected from C₁-C₄-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may be substituted by 1 or 2 identical or different substituents R^(x), wherein R^(x) is selected from CN and C(O)NH₂, and C₃-C₆-cycloalkyl, which may be unsubstituted or may be substituted by 1, 2 or 3 identical or different substituents R^(y), wherein R^(y) is selected from halogen, CN and C(O)NH₂. 